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1

Srinivasan, Rajini, Nataliya Nady, Neha Arora, Laura J. Hsieh, Tomek Swigut, Geeta J. Narlikar, Mark Wossidlo, and Joanna Wysocka. "Zscan4 binds nucleosomal microsatellite DNA and protects mouse two-cell embryos from DNA damage." Science Advances 6, no. 12 (March 2020): eaaz9115. http://dx.doi.org/10.1126/sciadv.aaz9115.

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Zinc finger protein Zscan4 is selectively expressed in mouse two-cell (2C) embryos undergoing zygotic genome activation (ZGA) and in a rare subpopulation of embryonic stem cells with 2C-like features. Here, we show that Zscan4 specifically recognizes a subset of (CA)n microsatellites, repeat sequences prone to genomic instability. Zscan4-associated microsatellite regions are characterized by low nuclease sensitivity and high histone occupancy. In vitro, Zscan4 binds nucleosomes and protects them from disassembly upon torsional strain. Furthermore, Zscan4 depletion leads to elevated DNA damage in 2C mouse embryos in a transcription-dependent manner. Together, our results identify Zscan4 as a DNA sequence–dependent microsatellite binding factor and suggest a developmentally regulated mechanism, which protects fragile genomic regions from DNA damage at a time of embryogenesis associated with high transcriptional burden and genomic stress.
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2

Ko, Shigeru B. H., Sakiko Azuma, Yukihiro Yokoyama, Akiko Yamamoto, Kazuhiro Kyokane, Shumpei Niida, Hiroshi Ishiguro, and Minoru S. H. Ko. "Inflammation increases cells expressing ZSCAN4 and progenitor cell markers in the adult pancreas." American Journal of Physiology-Gastrointestinal and Liver Physiology 304, no. 12 (June 15, 2013): G1103—G1116. http://dx.doi.org/10.1152/ajpgi.00299.2012.

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We have recently identified the zinc finger and SCAN domain containing 4 (Zscan4), which is transiently expressed and regulates telomere elongation and genome stability in mouse embryonic stem (ES) cells. The aim of this study was to examine the expression of ZSCAN4 in the adult pancreas and elucidate the role of ZSCAN4 in tissue inflammation and subsequent regeneration. The expression of ZSCAN4 and other progenitor or differentiated cell markers in the human pancreas was immunohistochemically examined. Pancreas sections of alcoholic or autoimmune pancreatitis patients before and under maintenance corticosteroid treatment were used in this study. In the adult human pancreas a small number of ZSCAN4-positive (ZSCAN4+) cells are present among cells located in the islets of Langerhans, acini, ducts, and oval-shaped cells. These cells not only express differentiated cell markers for each compartment of the pancreas but also express other tissue stem/progenitor cell markers. Furthermore, the number of ZSCAN4+cells dramatically increased in patients with chronic pancreatitis, especially in the pancreatic tissues of autoimmune pancreatitis actively regenerating under corticosteroid treatment. Interestingly, a number of ZSCAN4+cells in the pancreas of autoimmune pancreatitis returned to the basal level after 1 yr of maintenance corticosteroid treatment. In conclusion, coexpression of progenitor cell markers and differentiated cell markers with ZSCAN4 in each compartment of the pancreas may indicate the presence of facultative progenitors for both exocrine and endocrine cells in the adult pancreas.
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3

Dan, Jiameng, Zhongcheng Zhou, Fang Wang, Hua Wang, Renpeng Guo, David L. Keefe, and Lin Liu. "Zscan4 Contributes to Telomere Maintenance in Telomerase-Deficient Late Generation Mouse ESCs and Human ALT Cancer Cells." Cells 11, no. 3 (January 28, 2022): 456. http://dx.doi.org/10.3390/cells11030456.

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Proper telomere length is essential for indefinite self-renewal of embryonic stem (ES) cells and cancer cells. Telomerase-deficient late generation mouse ES cells and human ALT cancer cells are able to propagate for numerous passages, suggesting telomerase-independent mechanisms responding for telomere maintenance. However, the underlying mechanisms ensuring the telomere length maintenance are unclear. Here, using late generation telomerase KO (G4 Terc-/-) ESCs as a model, we show that Zscan4, highly upregulated in G4 Terc-/- ESCs, is responsible for the prolonged culture of these cells with stably short telomeres. Mechanistically, G4 Terc-/- ESCs showed reduced levels of DNA methylation and H3K9me3 at Zscan4 promoter and subtelomeres, which relieved the expression of Zscan4. Similarly, human ZSCAN4 was also derepressed by reduced H3K9me3 at its promoter in ALT U2 OS cells, and depletion of ZSCAN4 significantly shortened telomeres. Our results define a similar conserved pathway contributing to the telomere maintenance in telomerase-deficient late generation mESCs and human ALT U2OS cancer cells.
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4

Brown, Helen A., Charles A. C. Williams, Houjiang Zhou, Diana Rios-Szwed, Rosalia Fernandez-Alonso, Saria Mansoor, Liam McMulkin, et al. "An ERK5–KLF2 signalling module regulates early embryonic gene expression and telomere rejuvenation in stem cells." Biochemical Journal 478, no. 23 (December 6, 2021): 4119–36. http://dx.doi.org/10.1042/bcj20210646.

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The ERK5 MAP kinase signalling pathway drives transcription of naïve pluripotency genes in mouse Embryonic Stem Cells (mESCs). However, how ERK5 impacts on other aspects of mESC biology has not been investigated. Here, we employ quantitative proteomic profiling to identify proteins whose expression is regulated by the ERK5 pathway in mESCs. This reveals a function for ERK5 signalling in regulating dynamically expressed early embryonic 2-cell stage (2C) genes including the mESC rejuvenation factor ZSCAN4. ERK5 signalling and ZSCAN4 induction in mESCs increases telomere length, a key rejuvenative process required for prolonged culture. Mechanistically, ERK5 promotes ZSCAN4 and 2C gene expression via transcription of the KLF2 pluripotency transcription factor. Surprisingly, ERK5 also directly phosphorylates KLF2 to drive ubiquitin-dependent degradation, encoding negative feedback regulation of 2C gene expression. In summary, our data identify a regulatory module whereby ERK5 kinase and transcriptional activities bi-directionally control KLF2 levels to pattern 2C gene transcription and a key mESC rejuvenation process.
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5

Ruebel, Meghan L., Kailey A. Vincent, Peter Z. Schall, Kai Wang, and Keith E. Latham. "SMCHD1 terminates the first embryonic genome activation event in mouse two-cell embryos and contributes to a transcriptionally repressive state." American Journal of Physiology-Cell Physiology 317, no. 4 (October 1, 2019): C655—C664. http://dx.doi.org/10.1152/ajpcell.00116.2019.

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Embryonic genome activation (EGA) in mammals begins with transient expression of a large group of genes (EGA1). Importantly, entry into and exit from the 2C/EGA state is essential for viability. Dux family member genes play an integral role in EGA1 by activating other EGA marker genes such as Zscan4 family members. We previously reported that structural maintenance of chromosomes flexible hinge domain-containing protein 1 ( Smchd1) is expressed at the mRNA and protein levels in mouse oocytes and early embryos and that elimination of Smchd1 expression inhibits inner cell mass formation, blastocyst formation and hatching, and term development. We extend these observations here by showing that siRNA knockdown of Smchd1 in zygotes results in overexpression of Dux and Zscan4 in two-cell embryos, with continued overexpression of Dux at least through the eight-cell stage as well as prolonged expression of Zscan4. These results are consistent with a role for SMCHD1 in promoting exit from the EGA1 state and establishing SMCHD1 as a maternal effect gene and the first chromatin regulatory factor identified with this role. Additionally, bioinformatics analysis reveals that SMCHD1 also contributes to the creation of a transcriptionally repressive state to allow correct gene regulation.
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6

Zalzman, Michal, Geppino Falco, Lioudmila V. Sharova, Akira Nishiyama, Marshall Thomas, Sung-Lim Lee, Carole A. Stagg, et al. "Zscan4 regulates telomere elongation and genomic stability in ES cells." Nature 464, no. 7290 (March 24, 2010): 858–63. http://dx.doi.org/10.1038/nature08882.

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7

Lee, Sung-Lim, Geppino Falco, Ilaria Stanghellini, Uwem C. Bassey, Toshio Hamatani, and Minoru S. H. Ko. "Zscan4: A NOVEL GENE EXPRESSED EXCLUSIVELY IN LATE 2-CELL EMBRYOS." Biology of Reproduction 77, Suppl_1 (July 1, 2007): 79. http://dx.doi.org/10.1093/biolreprod/77.s1.79b.

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8

Portney, Benjamin A., Michal Arad, Aditi Gupta, Robert A. Brown, Raju Khatri, Phyo Nay Lin, Andrea M. Hebert, et al. "ZSCAN4 facilitates chromatin remodeling and promotes the cancer stem cell phenotype." Oncogene 39, no. 26 (June 2020): 4970–82. http://dx.doi.org/10.1038/s41388-020-1333-1.

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9

Tagliaferri, Daniela, Maria Teresa De Angelis, Nicola Antonino Russo, Maria Marotta, Michele Ceccarelli, Luigi Del Vecchio, Mario De Felice, and Geppino Falco. "Retinoic Acid Specifically Enhances Embryonic Stem Cell Metastate Marked by Zscan4." PLOS ONE 11, no. 2 (February 3, 2016): e0147683. http://dx.doi.org/10.1371/journal.pone.0147683.

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10

Nakai-Futatsugi, Yoko, and Hitoshi Niwa. "Zscan4 Is Activated after Telomere Shortening in Mouse Embryonic Stem Cells." Stem Cell Reports 6, no. 4 (April 2016): 483–95. http://dx.doi.org/10.1016/j.stemcr.2016.02.010.

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11

Sun, Hua, Pora Kim, Peilin Jia, Ae Kyung Park, Han Liang, and Zhongming Zhao. "Distinct telomere length and molecular signatures in seminoma and non-seminoma of testicular germ cell tumor." Briefings in Bioinformatics 20, no. 4 (March 20, 2018): 1502–12. http://dx.doi.org/10.1093/bib/bby020.

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AbstractTesticular germ cell tumors (TGCTs) are classified into two main subtypes, seminoma (SE) and non-seminoma (NSE), but their molecular distinctions remain largely unexplored. Here, we used expression data for mRNAs and microRNAs (miRNAs) from The Cancer Genome Atlas (TCGA) to perform a systematic investigation to explain the different telomere length (TL) features between NSE (n = 48) and SE (n = 55). We found that TL elongation was dominant in NSE, whereas TL shortening prevailed in SE. We further showed that both mRNA and miRNA expression profiles could clearly distinguish these two subtypes. Notably, four telomere-related genes (TelGenes) showed significantly higher expression and positively correlated with telomere elongation in NSE than SE: three telomerase activity-related genes (TERT, WRAP53 and MYC) and an independent telomerase activity gene (ZSCAN4). We also found that the expression of genes encoding Yamanaka factors was positively correlated with telomere lengthening in NSE. Among them, SOX2 and MYC were highly expressed in NSE versus SE, while POU5F1 and KLF4 had the opposite patterns. These results suggested that enhanced expression of both TelGenes (TERT, WRAP53, MYC and ZSCAN4) and Yamanaka factors might induce telomere elongation in NSE. Conversely, the relative lack of telomerase activation and low expression of independent telomerase activity pathway during cell division may be contributed to telomere shortening in SE. Taken together, our results revealed the potential molecular profiles and regulatory roles involving the TL difference between NSE and SE, and provided a better molecular understanding of this complex disease.
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12

Lee, Kyungwoo, and Lauren S. Gollahon. "Zscan4 interacts directly with human Rap1 in cancer cells regardless of telomerase status." Cancer Biology & Therapy 15, no. 8 (May 19, 2014): 1094–105. http://dx.doi.org/10.4161/cbt.29220.

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13

TAKAHASHI, Kazuki, Pablo J. ROSS, and Ken SAWAI. "The necessity of ZSCAN4 for preimplantation development and gene expression of bovine embryos." Journal of Reproduction and Development 65, no. 4 (2019): 319–26. http://dx.doi.org/10.1262/jrd.2019-039.

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14

Ishiguro, Kei-ichiro, Manuela Monti, Tomohiko Akiyama, Hiromi Kimura, Nana Chikazawa-Nohtomi, Miki Sakota, Saeko Sato, Carlo Alberto Redi, Shigeru B. H. Ko, and Minoru S. H. Ko. "Zscan4 is expressed specifically during late meiotic prophase in both spermatogenesis and oogenesis." In Vitro Cellular & Developmental Biology - Animal 53, no. 2 (October 3, 2016): 167–78. http://dx.doi.org/10.1007/s11626-016-0096-z.

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15

Eckersley-Maslin, Mélanie A., Valentine Svensson, Christel Krueger, Thomas M. Stubbs, Pascal Giehr, Felix Krueger, Ricardo J. Miragaia, et al. "MERVL/Zscan4 Network Activation Results in Transient Genome-wide DNA Demethylation of mESCs." Cell Reports 17, no. 1 (September 2016): 179–92. http://dx.doi.org/10.1016/j.celrep.2016.08.087.

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16

Pérez-Palacios, Raquel, María Climent, Javier Santiago-Arcos, Sofía Macías-Redondo, Martin Klar, Pedro Muniesa, and Jon Schoorlemmer. "YY2 in Mouse Preimplantation Embryos and in Embryonic Stem Cells." Cells 10, no. 5 (May 7, 2021): 1123. http://dx.doi.org/10.3390/cells10051123.

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Yin Yang 2 encodes a mammalian-specific transcription factor (YY2) that shares high homology in the zinc finger region with both YY1 and REX1/ZFP42, encoded by the Yin Yang 1 and Reduced Expression Protein 1/Zinc Finger Protein 42 gene, respectively. In contrast to the well-established roles of the latter two in gene regulation, X chromosome inactivation and binding to specific transposable elements (TEs), much less is known about YY2, and its presence during mouse preimplantation development has not been described. As it has been reported that mouse embryonic stem cells (mESC) cannot be propagated in the absence of Yy2, the mechanistic understanding of how Yy2 contributes to mESC maintenance remains only very partially characterized. We describe Yy2 expression studies using RT-PCR and staining with a high-affinity polyclonal serum in mouse embryos and mESC. Although YY2 is expressed during preimplantation development, its presence appears dispensable for developmental progress in vitro until formation of the blastocyst. Attenuation of Yy2 levels failed to alter either Zscan4 levels in two-cell embryos or IAP and MERVL levels at later preimplantation stages. In contrast to previous claims that constitutively expressed shRNA against Yy2 in mESC prohibited the propagation of mESC in culture, we obtained colonies generated from mESC with attenuated Yy2 levels. Concomitant with a decreased number of undifferentiated colonies, Yy2-depleted mESC expressed higher levels of Zscan4 but no differences in the expression of TEs or other pluripotency markers including Sox2, Oct4, Nanog and Esrrb were observed. These results confirm the contribution of Yy2 to the maintenance of mouse embryonic stem cells and show the preimplantation expression of YY2. These functions are discussed in relation to mammalian-specific functions of YY1 and REX1.
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17

Lee, Kyungwoo, and Lauren S. Gollahon. "ZSCAN4 and TRF1: A functionally indirect interaction in cancer cells independent of telomerase activity." Biochemical and Biophysical Research Communications 466, no. 4 (October 2015): 644–49. http://dx.doi.org/10.1016/j.bbrc.2015.09.107.

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18

Cheng, Zhou-Li, Meng-Li Zhang, Huai-Peng Lin, Chao Gao, Jun-Bin Song, Zhihong Zheng, Linpeng Li, et al. "The Zscan4-Tet2 Transcription Nexus Regulates Metabolic Rewiring and Enhances Proteostasis to Promote Reprogramming." Cell Reports 32, no. 2 (July 2020): 107877. http://dx.doi.org/10.1016/j.celrep.2020.107877.

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19

Dan, Jiameng, Philippe Rousseau, Swanand Hardikar, Nicolas Veland, Jiemin Wong, Chantal Autexier, and Taiping Chen. "Zscan4 Inhibits Maintenance DNA Methylation to Facilitate Telomere Elongation in Mouse Embryonic Stem Cells." Cell Reports 20, no. 8 (August 2017): 1936–49. http://dx.doi.org/10.1016/j.celrep.2017.07.070.

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20

Tian, Qing, and Li-quan Zhou. "Lactate Activates Germline and Cleavage Embryo Genes in Mouse Embryonic Stem Cells." Cells 11, no. 3 (February 4, 2022): 548. http://dx.doi.org/10.3390/cells11030548.

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Lactate was recently found to mediate histone lysine lactylation and facilitate polarization of M1 macrophages, indicating its role in metabolic regulation of gene expression. During somatic cell reprogramming, lactate promotes histone lactylation of pluripotency genes and improves reprogramming efficiency. However, the function of lactate in cell fate control in embryonic stem cells (ESCs) remains elusive. In this study, we revealed that lactate supplementation activated germline genes in mouse ESCs. Lactate also induced global upregulation of cleavage embryo genes, such as members of the Zscan4 gene family. Further exploration demonstrated that lactate stimulated H3K18 lactylation accumulation on germline and cleavage embryo genes, which in turn promoted transcriptional elongation. Our findings indicated that lactate supplementation expanded the transcriptional network in mouse ESCs.
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21

Sun, Yanmei, Fan Gao, Da Xu, Lei Lu, Qianggen Chen, Zheqing Yang, Xuenan Wang, and Xiaoyan Pan. "Wenshen Shengjing Decoction Improves Early Embryo Development by Maintaining Low H3K27me3 Levels in Sperm and Pronuclear Embryos of Spermatogenesis Impaired Mice." Evidence-Based Complementary and Alternative Medicine 2021 (September 27, 2021): 1–11. http://dx.doi.org/10.1155/2021/8035997.

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Many ingredients in Wenshen Shengjing Decoction (WSSJD) can cause epigenetic changes in the development of different types of cells. It is not yet known whether they can cause epigenetic changes in sperms or early embryos. Here, we investigated the role of WSSJD in epigenetic modifications of sperms or early embryos and early embryo development. A mouse model with spermatogenesis disorders was established with cyclophosphamide (CPA). WSSJD was administrated for 30 days. The male model mice after the treatment were mated with the female mice treated with superovulation. The embryo development rate of each stage was calculated. Immunofluorescence staining was used to detect the expression of H3K27me3 in sperm, pronuclear embryos, and 2-cell embryos. Western blotting was used to detect the expression of histone demethylase KDM6A and methyltransferase EZH2 in 2-cell embryos with developmental arrest. The expressions of zygotic genome activation genes (ZSCAN4, E1F1AX, HSPA1A, ERV4-2, and MYC) in 2-cell embryos with developmental arrest were analyzed with qRT-PCR. Comparing with the control group, CPA destroyed the development of seminiferous epithelium, significantly increased the expression level of H3K27me3 in sperm, reduced the expression ratio of H3K27me3 in female and male pronuclei, delayed the development of 2-cell embryos, and increased the developmental arrest rate and degeneration rate of 2-cell embryos. Moreover, the expressions of EZH2 and H3K27me3 were significantly increased in the 2-cell embryos with developmental arrest, and the expression of zygotic genome activation genes (ZSCAN4, E1F1AX, HSPA1A, ERV4-2, and MYC) was significantly decreased. Compared with the CPA group, WSSJD promoted the development of seminiferous epithelium, maintained a low level of H3K27me3 modification in sperm and male pronucleus, significantly increased the development rate of 2-cell embryos and 3-4 cell embryos, and reduced the developmental arrest rate and degeneration rate of 2-cell embryos. WSSJD may promote early embryonic development by maintaining a low level of H3K27me3 modification in sperm and male pronucleus and regulating the zygotic genome activation in mice with spermatogenesis disorders induced by CPA.
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Zhang, Qing, Wenjing Li, Pei Feng, Yayi Liu, Peng meng, Bo Chu, Jianglin Zhao, Yanxue Li, Yong Zhang, and Jun Liu. "Lnc5926 is essential for early embryonic development in goats through regulation of ZSCAN4 and EIF1AX." Theriogenology 180 (March 2022): 87–93. http://dx.doi.org/10.1016/j.theriogenology.2021.12.020.

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23

Falco, Geppino, Sung-Lim Lee, Ilaria Stanghellini, Uwem C. Bassey, Toshio Hamatani, and Minoru S. H. Ko. "Zscan4: A novel gene expressed exclusively in late 2-cell embryos and embryonic stem cells." Developmental Biology 307, no. 2 (July 2007): 539–50. http://dx.doi.org/10.1016/j.ydbio.2007.05.003.

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Portney, Benjamin A., Raju Khatri, W. Alex Meltzer, Jennifer M. Mariano, and Michal Zalzman. "ZSCAN4 is negatively regulated by the ubiquitin-proteasome system and the E3 ubiquitin ligase RNF20." Biochemical and Biophysical Research Communications 498, no. 1 (March 2018): 72–78. http://dx.doi.org/10.1016/j.bbrc.2018.02.155.

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25

Tanaka, Tetsuya S. "Transcriptional heterogeneity in mouse embryonic stem cells." Reproduction, Fertility and Development 21, no. 1 (2009): 67. http://dx.doi.org/10.1071/rd08219.

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The embryonic stem (ES) cell is a stem cell derived from early embryos that can indefinitely repeat self-renewing cell division cycles as an undifferentiated cell in vitro and give rise to all specialised cell types in the body. However, manipulating ES cell differentiation in vitro is a challenge due to, at least in part, heterogeneous gene induction. Recent experimental evidence has demonstrated that undifferentiated mouse ES cells maintained in culture exhibit heterogeneous expression of Dppa3, Nanog, Rex1, Pecam1 and Zscan4 as well as genes (Brachyury/T, Rhox6/9 and Twist2) normally expressed in specialised cell types. The Nanog-negative, Rex1-negative or T-positive ES cell subpopulation has a unique differentiation potential. Thus, studying the mechanism that generates ES cell subpopulations will improve manipulation of ES cell fate and help our understanding of the nature of embryonic development.
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Kwon, Yoo-Wook, Jae-Seung Paek, Hyun-Jai Cho, Choon-Soo Lee, Ho-Jae Lee, In-Hyun Park, Tae-Young Roh, et al. "Role of Zscan4 in secondary murine iPSC derivation mediated by protein extracts of ESC or iPSC." Biomaterials 59 (August 2015): 102–15. http://dx.doi.org/10.1016/j.biomaterials.2015.03.031.

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27

Barry, Raymond Mario, Olivia Sacco, Amel Mameri, Martin Stojaspal, William Kartsonis, Pooja Shah, Pablo De Ioannes, Ctirad Hofr, Jacques Côté, and Agnel Sfeir. "Rap1 regulates TIP60 function during fate transition between two-cell-like and pluripotent states." Genes & Development 36, no. 5-6 (February 24, 2022): 313–30. http://dx.doi.org/10.1101/gad.349039.121.

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In mammals, the conserved telomere binding protein Rap1 serves a diverse set of nontelomeric functions, including activation of the NF-kB signaling pathway, maintenance of metabolic function in vivo, and transcriptional regulation. Here, we uncover the mechanism by which Rap1 modulates gene expression. Using a separation-of-function allele, we show that Rap1 transcriptional regulation is largely independent of TRF2-mediated binding to telomeres and does not involve direct binding to genomic loci. Instead, Rap1 interacts with the TIP60/p400 complex and modulates its histone acetyltransferase activity. Notably, we show that deletion of Rap1 in mouse embryonic stem cells increases the fraction of two-cell-like cells. Specifically, Rap1 enhances the repressive activity of Tip60/p400 across a subset of two-cell-stage genes, including Zscan4 and the endogenous retrovirus MERVL. Preferential up-regulation of genes proximal to MERVL elements in Rap1-deficient settings implicates these endogenous retroviral elements in the derepression of proximal genes. Altogether, our study reveals an unprecedented link between Rap1 and the TIP60/p400 complex in the regulation of pluripotency.
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Bai, Lige, Lei Yang, Caiquan Zhao, Lishuang Song, Xuefei Liu, Chunling Bai, Guanghua Su, Zhuying Wei, and Guangpeng Li. "Histone Demethylase UTX is an Essential Factor for Zygotic Genome Activation and Regulates Zscan4 Expression in Mouse Embryos." International Journal of Biological Sciences 15, no. 11 (2019): 2363–72. http://dx.doi.org/10.7150/ijbs.34635.

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Akiyama, Tomohiko, Li Xin, Mayumi Oda, Alexei A. Sharov, Misa Amano, Yulan Piao, J. Scotty Cadet, et al. "Transient bursts of Zscan4 expression are accompanied by the rapid derepression of heterochromatin in mouse embryonic stem cells." DNA Research 22, no. 5 (August 31, 2015): 307–18. http://dx.doi.org/10.1093/dnares/dsv013.

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30

Ishiguro, Kei-ichiro, Yuhki Nakatake, Nana Chikazawa-Nohtomi, Hiromi Kimura, Tomohiko Akiyama, Mayumi Oda, Shigeru B. H. Ko, and Minoru S. H. Ko. "Expression analysis of the endogenous Zscan4 locus and its coding proteins in mouse ES cells and preimplantation embryos." In Vitro Cellular & Developmental Biology - Animal 53, no. 2 (October 3, 2016): 179–90. http://dx.doi.org/10.1007/s11626-016-0097-y.

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Jiang, Jing, Wenjian Lv, Xiaoying Ye, Lingbo Wang, Man Zhang, Hui Yang, Maja Okuka, et al. "Zscan4 promotes genomic stability during reprogramming and dramatically improves the quality of iPS cells as demonstrated by tetraploid complementation." Cell Research 23, no. 1 (November 13, 2012): 92–106. http://dx.doi.org/10.1038/cr.2012.157.

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32

Zhu, Yan, Ya-Hong Jiang, Ya-Ping He, Xuan Zhang, Zhao-Gui Sun, Man-Xi Jiang, and Jian Wang. "Knockdown of regulator of G-protein signalling 2 (Rgs2) leads to abnormal early mouse embryo development in vitro." Reproduction, Fertility and Development 27, no. 3 (2015): 557. http://dx.doi.org/10.1071/rd13269.

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Regulator of G-protein signalling 2 (Rgs2) is involved in G-protein-mediated signalling by negatively regulating the activity of the G-protein α-subunit. In the present study, the expression patterns of Rgs2 in mouse ovarian tissues and early embryos were determined by semiquantitative reverse transcription–polymerase chain reaction, immunohistochemistry and immunofluorescent analyses. Rgs2 expression was observed in the ovarian tissues of adult female mice, with an almost equal expression levels during different stages of the oestrous cycle. Rgs2 was abundant in the cytoplasm, membrane, nuclei and spindles of intact polar bodies in mouse early embryos at different developmental stages from the zygote to blastocyst. The effect of Rgs2 knockdown on early embryonic development in vitro was examined by microinjecting Rgs2-specific short interfering (si) RNAs into mouse zygotes. Knockdown of endogenous Rgs2 expression led to abnormal embryonic development in vitro, with a considerable number of early embryos arrested at the 2- or 4-cell stage. Moreover, mRNA expression of three zygotic gene activation-related genes (i.e. Zscan4, Tcstv1 and MuERV-L) was decreased significantly in 2-cell arrested embryos. These results suggest that Rgs2 plays a critical role in early embryo development.
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33

Storm, Michael P., Benjamin Kumpfmueller, Heather K. Bone, Michael Buchholz, Yolanda Sanchez Ripoll, Julian B. Chaudhuri, Hitoshi Niwa, David Tosh, and Melanie J. Welham. "Zscan4 Is Regulated by PI3-Kinase and DNA-Damaging Agents and Directly Interacts with the Transcriptional Repressors LSD1 and CtBP2 in Mouse Embryonic Stem Cells." PLoS ONE 9, no. 3 (March 3, 2014): e89821. http://dx.doi.org/10.1371/journal.pone.0089821.

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34

Hung, S. S. C., R. C. B. Wong, A. A. Sharov, Y. Nakatake, H. Yu, and M. S. H. Ko. "Repression of Global Protein Synthesis by Eif1a-Like Genes That Are Expressed Specifically in the Two-Cell Embryos and the Transient Zscan4-Positive State of Embryonic Stem Cells." DNA Research 20, no. 4 (May 5, 2013): 391–402. http://dx.doi.org/10.1093/dnares/dst018.

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35

Tagore, Somnath, Jovana Pavisic, Aaron T. Griffin, Katherine Janeway, Andrew L. Kung, Filemon Dela Cruz, Alejandro Sweet-Cordero, et al. "Abstract 488: A systems biology approach to defining tumor heterogeneity and prognostic and targetable master regulator protein signatures from bulk and single-cell RNAseq in osteosarcoma." Cancer Research 82, no. 12_Supplement (June 15, 2022): 488. http://dx.doi.org/10.1158/1538-7445.am2022-488.

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Abstract Despite many clinical trials, outcome for osteosarcoma (OS) patients remains poor, especially for those with metastatic or relapsed/refractory disease. We leveraged network-based systems biology approaches to discover Master Regulator (MR) proteins representing pharmacologically accessible, mechanistic determinants of OS cell state, and to dissect tumor transcriptional heterogeneity. MRs were identified by interrogating an OS regulatory network—generated from 87 RNAseq profiles in the TARGET OS cohort—with gene expression signatures from 149 diagnostic OS samples, using the VIPER algorithm. RNAseq profiles were generated in four sarcoma cell lines following perturbation with ~400 oncology drugs, and used to identify drugs capable of inverting MR activity profiles with the OncoTreat algorithm. Unsupervised, protein activity-based clustering of the samples identified two clusters, characterized by a significant overall survival difference (76% vs 38%, log-rank p-val 0.0041). Patients in the high-risk cluster presented aberrant activity of proteins involved in cell cycle (FOXM1, CENPF, TOP2A) and epigenetic remodeling (EZH2, KDM1A), while those in the low-risk cluster had aberrant activity of proteins involved in immune response (VAV1, CD86, CEBPE), interferon gama signaling (IRF5, MNDA), and senescence control (CREG1, TFEC). We further identified patients with metastatic disease and particularly poor outcome (<15% survival) showing high activity in stem cell-related proteins NANOG, ZSCAN4, and LIN28A. To address intra-tumor heterogeneity and immune infiltration (40-60% in the samples) in bulk RNAseq data, we inferred protein activity in previously published single-cell RNAseq profiles from 11 OS patients, using regulatory networks also produced by single-cell analysis. We identified three tumor subpopulations, co-existing in all the samples, with lineage similarity to osteoblasts, chondroblasts, and fibroblasts. The most active MR proteins (p-val < 10E-30) were highly distinct across these subpopulations: NANOG, REL, IGF2, TOP2A (osteoblasts), SSTR3, WNT1, KDM6B, EZH2 (chondroblasts), and NOD1, ERBB3, PRKDC, INSR (fibroblasts). Pharmacologically accessible MRs significantly active across the three subpopulations and in subsets of bulk RNAseq samples included EZH2, CDK2, TOP2A, HDAC5, and PRKDC. OncoTreat analysis predicted sensitivity to camptothecin, seliciclib, galunisertib, and rigosertib in both fibroblast- and chondroblast-like subpopulations. In conclusion, using network-based systems biology approaches in OS, we identified pharmacologically accessible MR subtypes differentiating survival at the bulk tissue level, and defining three distinct tumor subpopulations at the single-cell level with unique predicted drug sensitivities. Citation Format: Somnath Tagore, Jovana Pavisic, Aaron T. Griffin, Katherine Janeway, Andrew L. Kung, Filemon Dela Cruz, Alejandro Sweet-Cordero, Inge Behroozfard, Stanley Leung, Alex Lee, Darrell Yamashiro, Julia Glade Bender, Andrea Califano. A systems biology approach to defining tumor heterogeneity and prognostic and targetable master regulator protein signatures from bulk and single-cell RNAseq in osteosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 488.
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36

Kraus, Petra, Sivakamasundari V, Hong Bing Yu, Xing Xing, Siew Lan Lim, Thure Adler, Juan Antonio Aguilar Pimentel, et al. "Pleiotropic Functions for Transcription Factor Zscan10." PLoS ONE 9, no. 8 (August 11, 2014): e104568. http://dx.doi.org/10.1371/journal.pone.0104568.

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37

Dhasmana, Nitesh, Dalal Fadil, Anupama B. Kaul, and Jayan Thomas. "Investigation of nonlinear optical properties of exfoliated MoS2 using Photoacoustic Zscan." MRS Advances 1, no. 47 (2016): 3215–21. http://dx.doi.org/10.1557/adv.2016.456.

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ABSTRACTWe studied nonlinear absorption characteristics of exfoliated Molybdenum disulphide (MoS2) dispersion in 1-Methyl-2-pyrrolidinone and demonstrate a dual absorption characteristic at 532nm nanosecond pulsed laser wavelength. A number of recent reports demonstrate a saturable absorption in MoS2 and other 2D materials at low fluences and a deviation from this saturable absorption at higher fluence using open aperture Z scan (OZ scan) technique. It has been suggested that this deviation at higher fluences is due to nonlinear optical scattering. We have recently developed a new technique which combines OZ scan and photoacoustic Z-scan (PAZ-scan). It can measure photoacoustic and optical transmission signals simultaneously. The data obtained from both signals are employed to find nonlinear absorption parameters in non-linear optical materials. Our results reveal that non-linear scattering is not the cause of deviation of 2D materials from saturable absorption at higher fluences. We propose that the optical limiting behavior at higher fluence in these 2D materials is dominated by free carrier absorption.
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Chang, Qing. "Measurement of Nonlinear Properties for PEI Tetra Sulfonated Indium Phthalocyanine Compounds Self-Assembly Film Using Improved Tophat Z-Scan Technique." Materials Science Forum 895 (March 2017): 37–41. http://dx.doi.org/10.4028/www.scientific.net/msf.895.37.

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The nonlinear refraction and absorption properties of a PEI (phthalocyanine indium) tetrasulphonated chlorinated phthalocyanine electrostatic self-assembled film were studied using a simple and high sensitivity technique. We adopted picosecond laser pulses as source light and modified top-hat Zscan technique with a disk and a small aperture to explore the nonlinear refraction of the film. Experimental results show that the measuring sensitivity is increased by two orders of magnitude. Through theoretical fitting, we obtain the nonlinear refraction index and nonlinear absorption coefficients of the film are 2.1×10-14 m2/W and 2.4×10-7 m/W, respectively.
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39

Yanagihara, Yuta, Kazuki Inoue, Noritaka Saeki, Yuichiro Sawada, Shuhei Yoshida, Jiwon Lee, Tadahiro Iimura, and Yuuki Imai. "Zscan10 suppresses osteoclast differentiation by regulating expression of Haptoglobin." Bone 122 (May 2019): 93–100. http://dx.doi.org/10.1016/j.bone.2019.02.011.

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40

Pathrose, Bini, V. P. N. Nampoori, P. Radhakrishnan, and A. Mujeeb. "Investigations on the third order nonlinear optical properties of Basic Fuchsin dye using zscan technique." Optik 127, no. 19 (October 2016): 7717–25. http://dx.doi.org/10.1016/j.ijleo.2016.05.136.

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41

Skamagki, Maria, Cristina Correia, Percy Yeung, Timour Baslan, Samuel Beck, Cheng Zhang, Christian A. Ross, et al. "ZSCAN10 expression corrects the genomic instability of iPSCs from aged donors." Nature Cell Biology 19, no. 9 (August 28, 2017): 1037–48. http://dx.doi.org/10.1038/ncb3598.

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42

Liu, Wentao, Jiaxuan Zou, Rijun Ren, Jingping Liu, Gentang Zhang, and Maokai Wang. "A Novel 10-Gene Signature Predicts Poor Prognosis in Low Grade Glioma." Technology in Cancer Research & Treatment 20 (January 1, 2021): 153303382199208. http://dx.doi.org/10.1177/1533033821992084.

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Aim: Low grade glioma (LGG) is a lethal brain cancer with relatively poor prognosis in young adults. Thus, this study was performed to develop novel molecular biomarkers to effectively predict the prognosis of LGG patients and finally guide treatment decisions. Methods: survival-related genes were determined by Kaplan-Meier survival analysis and multivariate Cox regression analysis using the expression and clinical data of 506 LGG patients from The Cancer Genome Atlas (TCGA) database and independently validated in a Chinese Glioma Genome Atlas (CGGA) dataset. A prognostic risk score was established based on a linear combination of 10 gene expression levels using the regression coefficients of the multivariate Cox regression models. GSEA was performed to analyze the altered signaling pathways between the high and low risk groups stratified by median risk score. Results: We identified a total of 1489 genes significantly correlated with patients’ prognosis in LGG. The top 5 protective genes were DISP2, CKMT1B, AQP7, GPR162 and CHGB, the top 5 risk genes were SP1, EYA3, ZSCAN20, ITPRIPL1 and ZNF217 in LGG. The risk score was predictive of poor overall survival and relapse-free survival in LGG patients. Pathways of small cell lung cancer, pathways in cancer, chronic myeloid leukemia, colorectal cancer were the top 4 most enriched pathways in the high risk group. SP1, EYA3, ZSCAN20, ITPRIPL1, ZNF217 and GPR162 were significantly up-regulated, while DISP2, CKMT1B, AQP7 were down-regulated in 523 LGG tissues as compared to 1141 normal brain controls. Conclusions: The 10-gene signature may become novel prognostic and diagnostic biomarkers to considerably improve the prognostic prediction in LGG.
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Li, Zhihua, Cheng Pan, Zhibo Wang, Xiaheng Deng, Quan Zhu, Weibing Wu, and Liang Chen. "LncRNA PCBP1-AS1 correlated with the functional states of cancer cells and inhibited lung adenocarcinoma metastasis by suppressing the EMT progression." Carcinogenesis 42, no. 7 (June 9, 2021): 931–39. http://dx.doi.org/10.1093/carcin/bgab047.

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Abstract The development of single-cell RNA sequencing (scRNA-seq) provided us an unprecedented chance to identify novel oncogenes or tumor suppressors at single-cell resolution. Long non-coding RNAs (lncRNAs) related to the functional states of cancer cells might play vital roles in the progression of lung adenocarcinoma (LUAD). In this study, lncRNAs that were associated with the functional states of LUAD cells identified in scRNA-seq studies were screened based on the CancerSEA database. Differential gene expression analysis and survival analysis were performed in TCGA, GEO and our JSPH databases. Finally, transwell and tail vein metastasis assays were used to reveal the functions of our identified novel prognostic lncRNAs. A total of 849 lncRNAs were initially identified. Among them, 11 lncRNAs were found significantly associated with LUAD prognosis in the TCGA database. Two of them (PCBP1-AS1 and ZSCAN16-AS1) were further validated in independent GEO datasets. ScRNA-seq analysis showed that PCBP1-AS1 and ZSCAN16-AS1 were significantly negatively correlated with most of the functional states of LUAD cells, especially with metastasis. Functionally, PCBP1-AS1 was aberrantly downregulated in LUAD cells and tumor tissues. Knockdown of PCBP1-AS1 significantly promoted the migration and invasion of LUAD cells. Consistently, PCBP1-AS1 overexpression suppressed the metastasis of LUAD in vitro and in vivo. Besides, PCBP1-AS1 inhibition induced decreased E-cadherin expression and increased N-cadherin, Vimentin and Snail expression. In conclusion, PCBP1-AS1 could suppress the metastasis of LUAD by targeting the epithelial–mesenchymal transition pathway and might serve as a prognostic biomarker and a potential therapeutic target of LUAD.
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Yamane, Mariko, Setsuko Fujii, Satoshi Ohtsuka, and Hitoshi Niwa. "Zscan10 is dispensable for maintenance of pluripotency in mouse embryonic stem cells." Biochemical and Biophysical Research Communications 468, no. 4 (December 2015): 826–31. http://dx.doi.org/10.1016/j.bbrc.2015.11.039.

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Ogawa, Seiji, Mitsutoshi Yamada, Akihiro Nakamura, Tohru Sugawara, Akari Nakamura, Shoko Miyajima, Yuichirou Harada, et al. "Zscan5b Deficiency Impairs DNA Damage Response and Causes Chromosomal Aberrations during Mitosis." Stem Cell Reports 12, no. 6 (June 2019): 1366–79. http://dx.doi.org/10.1016/j.stemcr.2019.05.002.

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46

Bárcena, Clea, and Carlos López-Otín. "A fruitful liaison of ZSCAN10 and ROS on the road to rejuvenation." Nature Cell Biology 19, no. 9 (August 31, 2017): 1012–13. http://dx.doi.org/10.1038/ncb3602.

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47

Eguchi, Takanori, Thomas L. Prince, Manh Tien Tran, Chiharu Sogawa, Benjamin J. Lang, and Stuart K. Calderwood. "MZF1 and SCAND1 Reciprocally Regulate CDC37 Gene Expression in Prostate Cancer." Cancers 11, no. 6 (June 8, 2019): 792. http://dx.doi.org/10.3390/cancers11060792.

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Cell division control 37 (CDC37) increases the stability of heat shock protein 90 (HSP90) client proteins and is thus essential for numerous intracellular oncogenic signaling pathways, playing a key role in prostate oncogenesis. Notably, elevated expression of CDC37 was found in prostate cancer cells, although the regulatory mechanisms through which CDC37 expression becomes increased are unknown. Here we show both positive and negative regulation of CDC37 gene transcription by two members of the SREZBP-CTfin51-AW1-Number 18 cDNA (SCAN) transcription factor family—MZF1 and SCAND1, respectively. Consensus DNA-binding motifs for myeloid zinc finger 1 (MZF1/ZSCAN6) were abundant in the CDC37 promoter region. MZF1 became bound to these regulatory sites and trans-activated the CDC37 gene whereas MZF1 depletion decreased CDC37 transcription and reduced the tumorigenesis of prostate cancer cells. On the other hand, SCAND1, a zinc fingerless SCAN box protein that potentially inhibits MZF1, accumulated at MZF1-binding sites in the CDC37 gene, negatively regulated the CDC37 gene and inhibited tumorigenesis. SCAND1 was abundantly expressed in normal prostate cells but was reduced in prostate cancer cells, suggesting a potential tumor suppressor role of SCAND1 in prostate cancer. These findings indicate that CDC37, a crucial protein in prostate cancer progression, is regulated reciprocally by MZF1 and SCAND1.
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48

Ma, Shuang, Yang Zheng, and Chengwei Fei. "Identification of key factors associated with early- and late-onset ovarian serous cystadenocarcinoma." Future Oncology 16, no. 34 (December 2020): 2821–33. http://dx.doi.org/10.2217/fon-2020-0668.

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Aim: To uncover the molecular mechanisms of early-onset ovarian serous cystadenocarcinoma (EOOSC; patients <50 years old) and late-onset ovarian serous cystadenocarcinoma (LOOSC; patients ≥50 years old). Materials & methods: Bioinformatics was utilized to identify the key factors. Results: 478 EOOSC and 899 LOOSC individual differentially expressed genes were identified and enriched in different pathways. The expression of key genes LAG3, LRRC63 and MT1B significantly influenced the overall survival of EOOSC patients. The expression of key genes RDH12, NTSR1, ZSCAN16, CT45A3 and EPPIN_WFDC6 significantly affected the overall survival of LOOSC patients. Conclusions: The molecular mechanisms of EOOSC and LOOSC appear to be different, so that patients might be treated individually in respect of age.
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Skamagki, Maria, Cristina Correia, Percy Yeung, Timour Baslan, Samuel Beck, Cheng Zhang, Christian A. Ross, et al. "Author Correction: ZSCAN10 expression corrects the genomic instability of iPSCs from aged donors." Nature Cell Biology 21, no. 4 (January 14, 2019): 531–32. http://dx.doi.org/10.1038/s41556-018-0269-y.

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50

Clough, Richard Lee, Georgia Dermentzaki, and Leonidas Stefanis. "Functional dissection of the α-synuclein promoter: transcriptional regulation by ZSCAN21 and ZNF219." Journal of Neurochemistry 110, no. 5 (September 2009): 1479–90. http://dx.doi.org/10.1111/j.1471-4159.2009.06250.x.

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