Articles de revues : « Cell state »

1

Holden, C. « STATE STEM CELL INITIATIVES : Most State Stem Cell Efforts Staying Afloat ». Science 323, n^o 5922 (27 mars 2009) : 1660b—1661b. http://dx.doi.org/10.1126/science.323.5922.1660b.

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Mishra, Dharma Niranjan. « Clinico- haematological Profile of Sickle Cell Disease and Sickle Cell BetaThalassaemia in the State of Odisha ». Journal of Medical Science And clinical Research 05, n^o 06 (12 juin 2017) : 23062–69. http://dx.doi.org/10.18535/jmscr/v5i6.44.

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José Mendes de Seixas, Falcondes, Juan Paulo Robles Balestero, Claudiner Mendes de Seixas, Fernando Lessa Tofoli et Grover Victor Torrico-Bascopé. « Bridgeless boost PFC converter using the three-state switching cell ». Eletrônica de Potência 17, n^o 2 (1 mai 2012) : 513–20. http://dx.doi.org/10.18618/rep.2012.2.513520.

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Aalam, Syed Mohammed Musheer, Kannan Vrindavan Manian, Sumitha Prameela Bharathan, Thiyagaraj Mayuranathan et Shaji Ramachandran Velayudhan. « Identification of Stable OCT4+NANOG− State in Somatic Cell Reprogramming ». Cellular Reprogramming 18, n^o 6 (décembre 2016) : 367–68. http://dx.doi.org/10.1089/cell.2016.0018.

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Pauklin, Siim, et Ludovic Vallier. « The Cell-Cycle State of Stem Cells Determines Cell Fate Propensity ». Cell 155, n^o 1 (septembre 2013) : 135–47. http://dx.doi.org/10.1016/j.cell.2013.08.031.

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Pauklin, Siim, et Ludovic Vallier. « The Cell-Cycle State of Stem Cells Determines Cell Fate Propensity ». Cell 156, n^o 6 (mars 2014) : 1338. http://dx.doi.org/10.1016/j.cell.2014.02.044.

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Lai, Dongmei, Yifei Chen, Fangyuan Wang, Lizhen Jiang et Chunsheng Wei. « LKB1 Controls the Pluripotent State of Human Embryonic Stem Cells ». Cellular Reprogramming 14, n^o 2 (avril 2012) : 164–70. http://dx.doi.org/10.1089/cell.2011.0068.

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Smaglik, Paul. « Stem-cell state lines ». Nature 429, n^o 6994 (juin 2004) : 905. http://dx.doi.org/10.1038/nj6994-905a.

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Venugopal, V. « Solid state electrochemical cell ». Progress in Crystal Growth and Characterization of Materials 45, n^o 1-2 (janvier 2002) : 139–41. http://dx.doi.org/10.1016/s0960-8974(02)00039-6.

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McNiven, M. A. « The solid state cell ». Biology of the Cell 94, n^o 9 (décembre 2002) : 555–56. http://dx.doi.org/10.1016/s0248-4900(02)01203-0.

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Donnenberg, Albert D., James B. Hicks, Michael Wigler et Vera S. Donnenberg. « The cancer stem cell : Cell type or cell state ? » Cytometry Part A 83A, n^o 1 (18 octobre 2012) : 5–7. http://dx.doi.org/10.1002/cyto.a.22208.

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Canipari, Rita. « Cell–cell interaction and oocyte growth ». Zygote 2, n^o 4 (novembre 1994) : 343–45. http://dx.doi.org/10.1017/s0967199400002173.

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In most mammals, oocytes initiate meiosis in late fetal life; by the time of birthe they have already entered the diplotene stage of prophase I of meiosis and becaome arrested thereafter at the dictyate state(Baker, 1972). At this stage they became surrounded by a few nonproliferating flat follicle cells forming a unit called the resting or primordial follicle.

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Jochem, Frank J. « Probing the physiological state of phytoplankton at the single-cell level ». Scientia Marina 64, n^o 2 (30 juin 2000) : 183–95. http://dx.doi.org/10.3989/scimar.2000.64n2183.

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Feng, Fangshuo, Hao Sun, Xiaoyu Zhang, Xiyue Sun, Tengteng Yu, Haiqing Xiong, Gang An, Lu-Gui Qiu et Mu Hao. « Single-Cell Multi-Omics Analysis Reveals Heterogeneity of Malignant Plasma Cell during Progression of Multiple Myeloma ». Blood 144, Supplement 1 (5 novembre 2024) : 6845. https://doi.org/10.1182/blood-2024-203100.

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Multiple myeloma is a malignant plasma cell disease of the bone marrow, MM have a relatively benign stage of MGUS, which further progresses to SMM and eventually progresses to active MM, MM undergoes extramedullary invasion evolving into PCL, Heterogeneity analysis of plasma cells in these four phases facilitates our understanding of this evolution and the targeting of therapies. A total of bone marrow samples from healthy controls (n=7) and patients with MGUS (n=2), SMM (n=5), MM (n=6), and PCL (n=2) were enrolled in this study for bone marrow single-cell multi-omics sequencing of bone marrow mononuclear cells (BMNCs), Based on the expression of genes characterizing each cell subpopulation, we define 10 cell types including plasma cells. Firstly, in order to elucidate the molecular expression characteristics of plasma cells and MM cells in each stage, we Identify malignant plasma cells from all plasma cells using inferCNV, which led to the identification of malignant plasma cells in each stage. Further subcluster analysis revealed significant disease stage heterogeneity of MM cells in patients with different disease stages such as MGUS, SMM, MM, and PCL, and MM cell heterogeneity gradually increased with disease progression. We also found that the proportion of malignant plasma cells with similar transcriptional characteristics to normal plasma cells gradually decreased from MGUS to PCL. GSVA analysis of the 4 stages of MM cells confirmed that the molecular features of MM cells in the MGUS and SMM stages are similar, molecular features in the MM and PCL stages are similar too. The UAMS70 gene set allows scoring of the degree of malignancy of MM cells, the degree of malignancy is determined based on the score, we observe a slow increase in the malignancy of plasma cells from MGUS to MM stage, but from MM to PCL stage showed a sharp increase, and, the SMM stage has a relatively similar proportion of malignant plasma cells with transcriptional similarity to normal plasma cells. Cytotrace shows a gradual increase in the differentiation capacity of malignant plasma cells from MGUS to PCL stage. In a cell trajectory analysis of malignant plasma cells from MGUS to PCL, it is found that cell development is divided into nine states, the more important of which are state 1, state 2, and state 8, and that there are significant differences in the distribution of the stages from MGUS to PCL both in terms of disease stage and between patients. State 2 has cells with low differentiation capacity, state 1 and state 8 have high differentiation capacity, MGUS and SMM are mainly distributed in state 2 and state 8, and PCL is distributed in state 8 and state 1. It is noteworthy that one of the 2 patients with PCL has cells completely distributed in state 1, and the other completely in state 8, indicating that even though there are differences in transcriptome expression, the cell trajectory of PCL cells from the same patient are similar. This indicates that even though there are differences in transcriptome expression, the cell trajectory distribution of the cells of the same patient in PCL is similar, and from the MGUS to the PCL, the cells of each patient tend to be more and more distributed mainly in one branch. Next, the HALLMARK gene set is used to score each state, and it is found that DNA damage repair, G2M checkpoint, immune response, and glycolysis pathways are enriched in all three states, suggesting that malignant plasma cells are activated with proliferative capacity and stimulate the immune response at all stages, and that glycolytic metabolism plays an important role. Notably, two PCL patients showed different states, one with activation of the p53 pathway and IL6-JAK-STAT3 pathway, and the other with activation of the MYC pathway and NOTCH pathway, suggesting the diversity of mechanisms driving PCL invasion in the patients. Moreover, it is found that some cells at the MGUS, SMM, and MM stages are already in the PCL state branch, suggesting that even at the early stage of the disease, some cells have already reached a more malignant state. VDJ analysis shows that the proportion of clonal plasma cells increases from the MGUS to the PCL stage, and single clone appears in multiple clusters, suggesting that even malignant plasma cells of the same clone differ greatly at the level of gene expression. In summary, we find that the heterogeneity of plasma cells is evident in all aspects.

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Winter, Jörg, et Peter Brandt. « Stage-Specific State I-State II Transitions during the Cell Cycle of Euglena gracilis ». Plant Physiology 81, n^o 2 (1 juin 1986) : 548–52. http://dx.doi.org/10.1104/pp.81.2.548.

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Park, Joonghoon, Chul Kim, Yong Tang, Tomokazu Amano, Chih-Jen Lin et X. Cindy Tian. « Reprogramming of Mouse Fibroblasts to an Intermediate State of Differentiation by Chemical Induction ». Cellular Reprogramming 13, n^o 2 (avril 2011) : 121–31. http://dx.doi.org/10.1089/cell.2010.0067.

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17

Kondor-Koch, C. « State-of-the-art cell fusion cell fusion ». Trends in Biochemical Sciences 12 (janvier 1987) : 379–80. http://dx.doi.org/10.1016/0968-0004(87)90177-0.

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Root, Alex. « Do cells use passwords in cell-state transitions ? Is cell signaling sometimes encrypted ? » Theory in Biosciences 139, n^o 1 (7 juin 2019) : 87–93. http://dx.doi.org/10.1007/s12064-019-00295-1.

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Thomas, Jonathan. « California : ‘the Stem Cell State’ ». Regenerative Medicine 6, n^o 6s (novembre 2011) : 113–15. http://dx.doi.org/10.2217/rme.11.79.

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Myung, Kyungjae. « Targeting the cancer cell state ». Cell Cycle 14, n^o 15 (7 juillet 2015) : 2385–86. http://dx.doi.org/10.1080/15384101.2015.1063294.

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21

Christofk, Heather. « Metabolic Regulation of Cell State ». Free Radical Biology and Medicine 128 (novembre 2018) : S13. http://dx.doi.org/10.1016/j.freeradbiomed.2018.10.390.

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Cesar Dias, Julio, et Telles Brunelli Lazzarin. « Boost dc-dc Converter with Switched-Capacitor and Four-state Switching Cell ». Eletrônica de Potência 27, n^o 03 (30 septembre 2022) : 1–12. http://dx.doi.org/10.18618/rep.2022.3.0023.

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Joseph (BSc MSc, PhD), Ekhator Edehia, Jemikalajah Daniel Johnson (BSc MSc, PhD), Anie Clement Oliseloke (B Pharm MSc, PhD) et Okungbowa Awo Michael (BSc MSc, PhD). « Prevalence of Gastrointestinal Parasites among Sickle Cell Patients in Delta State, Nigeria ». International Journal Of Pharmaceutical And Bio-Medical Science 03, n^o 01 (30 janvier 2023) : 18–28. http://dx.doi.org/10.47191/ijpbms/v3-i1-04.

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Sickle cell anemia crisis and death in the under-developed nations constitute one of the most challenging global public health problems. It is estimated that each year out of the three hundred thousand babies born worldwide with severe forms of hemoglobin disorders, sickle cell disease constitute more than half of this figure. Sickle cell disorder is an abnormal hemoglobin condition caused by the inheritance of abnormal hemoglobin (Hbs) genes from both parents. This study was aimed at determining the prevalence of gastrointestinal parasites among sickle cell subjects in Delta State. Stool samples were collected from a total of 320 subjects, 160 each from Delta South (Warri) and Delta North (Agbor). Questionnaires and informed consent forms were given to the subjects that are of age and to the parents of the minors before sample collection. The stool samples were examined both macroscopically and microscopically for gastrointestinal parasites .InWarri, 40% (64/160) of SCA subjects infected with either gastrointestinal heamoparisites were male, while 48.1% were females. In Agbor, 47.5% were males, while 43.8% were females. This was statistically significant (p< 0.05). The greatest frequency of infection was observed in SCA subjects within the age bracket of 1-10. (42.5%) in warri and 56.2%atAgbor. In Warri A.lumbricoides, hookworm, T.trichuria, E coliand malaria parasites were observed, 18.1%, 5.6%, 2.5%, 1.3% and 60.6% respectively among sickle cell subjects infected with either gastrointestinal haemoparasites. No microfilaria was isolated among subjects in warri, but was isolated at Agbor (0.6%).Also at Agbor, A. lumbricoides, hookworm, T.trichuria, E. coli,and malaria parasites had prevalence of16.8%, 2.5%, 1.3%, 1.9% and 68.1%respectively. In Warri, SCA subjects without parasitic infection have a mean PCV of 23.27% as against those with parasitic infection having a mean PCV of 12.88%. At Agbor, those without infection have a mean PCV of 22.84% as against 19.72% among those with parasitic infection. Among SCA subjects with either gastrointestinal or haemoparasites in warri, 24.4%, 50.0% 13.7% resides in rural, urban and riverine Communities respectively. At Agbor 60%, 31.3% resides in rural & urban communities respectively. The prevalence of infection among those who deworm always, occasionally only and those who never deworm were 32.5%, 53.1% and 2.5% respectively in Warri and, 10%, 60% & 21.3% respectively in Agbor. All sampled SCA subjects received blood transfusion always or occasionally as 70.6% and 17.8% respectively in Warri, as 85.0% and 6.3% respectively in Agbor. Prevalence of infection among subjects who use water closet and latrine were 18.7% and 6.9% respectively. Subjects who never wash their hands before and after eating have prevalence of 7.2% while those who wash their hands before and after eating always were 18.4%. The prevalence of malaria parasites 60.6% and 66.8%, Warri and Agbor respectively. Overall, the prevalence of parasitic infections among SCA subjects in Warri was 88.1%. Of this 48.1% were females.SCA subjects between the ages of 1-10 were mostly infected. A. lumbricoides (18.1%) was the gastrointestinal parasite mostly isolated. This study concludes that prevalence of gastrointestinal and haemoparasite among sickle cell subjects is very high in Delta State. Therefore, the need for all sickle cell anemic subjects to strictly use insecticide treated nets is highly advocated.

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Zhou, Da, Dingming Wu, Zhe Li, Minping Qian et Michael Q. Zhang. « Population dynamics of cancer cells with cell state conversions ». Quantitative Biology 1, n^o 3 (17 juin 2013) : 201–8. http://dx.doi.org/10.1007/s40484-013-0014-2.

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Choi, Kwang-Hwan, Dong-Kyung Lee, Jong-Nam Oh, Hye-Young Son et Chang-Kyu Lee. « FGF2 Signaling Plays an Important Role in Maintaining Pluripotent State of Pig Embryonic Germ Cells ». Cellular Reprogramming 20, n^o 5 (octobre 2018) : 301–11. http://dx.doi.org/10.1089/cell.2018.0019.

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Wang, Xiukun, et Jinsong Li. « An intermediate cell state allows rerouting of cell fate ». Journal of Biological Chemistry 292, n^o 46 (17 novembre 2017) : 19133–34. http://dx.doi.org/10.1074/jbc.h117.812537.

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Gillich, Astrid, et Katsuhiko Hayashi. « Switching stem cell state through programmed germ cell reprogramming ». Differentiation 81, n^o 5 (juin 2011) : 281–91. http://dx.doi.org/10.1016/j.diff.2011.01.003.

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Hiroshima, Michio, et Yasushi Sako. « 3P180 Cell signaling occurs by a specific mobility and clustering state of epidermal growth factor receptor(12. Cell biology,Poster) ». Seibutsu Butsuri 53, supplement1-2 (2013) : S241. http://dx.doi.org/10.2142/biophys.53.s241_5.

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Hirusaki, Kotoe, et Yoshihiro Ohta. « 2P188 Monitoring of energy state of cells during cell division(12. Cell biology,Poster) ». Seibutsu Butsuri 53, supplement1-2 (2013) : S190. http://dx.doi.org/10.2142/biophys.53.s190_2.

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Decombis, Salomé, Johannes Smolander, Jonas Bouhlal, Jay Klievink, Hanna Lähteenmäki, Emmi Jokinen, Linh Lin et al. « Bone Marrow Stromal Cells Hamper Leukemia Cell Induced NK Cell Activation and Cytotoxicity ». Blood 144, Supplement 1 (5 novembre 2024) : 4814. https://doi.org/10.1182/blood-2024-202959.

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Natural killer (NK) cells are emerging as a promising therapeutic option in hematological malignancies including acute myeloid leukemia (AML). However, the complete eradication of AML cells from the bone marrow (BM) represents a major clinical challenge. The BM stromal microenvironment plays an important role in AML cells' survival and resistance to chemotherapy, whereas the impact of stromal cells on NK cell function has not yet been fully discovered. To decipher the molecular modulations that occur in the BM stromal niche inducing AML cell resistance to NK cell attack, we performed functional co-cultures of NK, AML and stromal cells. We designed a co-culture system mimicking the BM stromal compartment using HS-5 stromal cells and 3 AML (MOLM-14, OCI-M1 and THP-1) and 1 CML (K562) cell lines. After culturing leukemia cells with HS-5 cells for 24h, primary expanded NK cells were added, and the viability of the tumor cells was measured by flow cytometry after 24h. To understand how NK and leukemia cells respond to their interaction within the stromal microenvironment, we performed single-cell RNA sequencing (scRNA-seq), genome-scale loss-of-function CRISPR screen and analysis of secreted soluble factors. After 24h of pre-stimulation of leukemia cells with HS-5 cells and 24h of culture with NK cells, we observed reduced killing of target leukemia cells in the presence of stromal cells compared to NK cell and target cell alone conditions (viability of K562 cells: 46 vs 38%, p=0.0130; MOLM-14: 63 vs 48%, p=0.0165; OCI-M1: 56 vs 35%, p=0.0163, and THP-1: 58 vs 33% p=0.0394). The analysis of soluble factors revealed an increase of CCL2, G-CSF, GM-CSF, IL-1β, IL-4, IL-6, IL-8 and IL-10 when tumor and NK cells interacted within the stromal niche suggesting a role of these soluble mediators in the resistance of leukemic cells. Interestingly, genome-scale CRISPR screen also identified the loss of IL-10 gene as a sensitizer of THP-1 cells to NK cell mediated-cytotoxicity in the stromal microenvironment. To understand the dynamic changes that happen in various cell types during the co-culture, we pooled all different scRNA-seq conditions together and performed an unsupervised clustering separating expanded NK, leukemia and HS-5 cells. The co-culture with K562 CML cells induced an activated state (73%) of NK cells characterized by the expression of TNFRSF9 (4-1BB), TNFRSF18 (GITR), HAVCR2 (TIM-3) and TIGIT, whereas co-culture with MOLM-14 cells did not induce strong NK cell activation (58% of cells were in the resting state). The co-culture with OCI-M1 (47%) and THP1 (68%) cells led to an activated type I interferon (IFN) state (OAS1, OAS2, MX1, MX2, ISG15) in NK cells. Stromal cells induced a distinct NK cell phenotype characterized by the activation of the IL2/STAT5 and apoptosis signaling and a decrease of the NK cell activation receptor NKp30 expression and an increase of exhaustion markers TIM-3 and TIGIT. Furthermore, during NK, leukemia (K562, MOLM-14 or THP-1) and stromal cells co-culture, an increase of the TGFβ, IL-6/JAK/STAT3, TNFα/NFKB and hypoxia signaling was observed in NK cells. In addition, a decrease of the activated (73 vs 31% in NK with K562 cells) and type I IFN state of NK cells (68 vs 6% in NK with THP-1 cells) was highlighted when stromal cells were present. In K562, THP-1 and MOLM-14 tumor cells, the interaction with the stromal cells decreased NK cell-induced IFNα and IFNγ response resulting in the downregulation of MHC class I (HLA-B, HLA-F) and class II (HLA-DMB, HLA-DQA1, HLA-DRA) genes. A decrease of TNFα pathway and a downregulation of IL-32 was also observed in the tumor cells. As a common mechanism in all tumor cells, including OCI-M1 cells, we noted an induction of TGFβ and downregulation of the IL-6/JAK/STAT3 signaling resulting in the resistance to NK cells. Collectively, at single-cell resolution, our findings reveal the dynamic transcriptomic changes and soluble dialogue of tumor and NK cells interacting within the stromal BM niche. Based on our findings, stromal cells impact both NK cells hampering their activation potential and tumor cells making them more resistant to NK mediated cytotoxicity. This highlights the need for potential combination therapies to enhance the efficacy of NK cell-based treatments in AML.

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Park, Tae-Yeong, Kwang-Hwan Choi, Dong-Kyung Lee, Jong-Nam Oh, Seung-Hun Kim et Chang-Kyu Lee. « Attempting to Convert Primed Porcine Embryonic Stem Cells into a Naive State Through the Overexpression of Reprogramming Factors ». Cellular Reprogramming 20, n^o 5 (octobre 2018) : 289–300. http://dx.doi.org/10.1089/cell.2017.0071.

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Pullen, Lara C. « Stem Cell Derived Beta Cells : The State of the Science ». American Journal of Transplantation 16, n^o 11 (27 octobre 2016) : 3067–68. http://dx.doi.org/10.1111/ajt.14068.

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Liao, Pin-Chao, Emily J. Yang et Liza A. Pon. « Live-Cell Imaging of Mitochondrial Redox State in Yeast Cells ». STAR Protocols 1, n^o 3 (décembre 2020) : 100160. http://dx.doi.org/10.1016/j.xpro.2020.100160.

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Wen, Jessica H., Justin R. Tse et Adam J. Engler. « Mesenchymal Stem Cells Duro- and Hapto- Taxis Alters Cell State ». Biophysical Journal 102, n^o 3 (janvier 2012) : 706a. http://dx.doi.org/10.1016/j.bpj.2011.11.3831.

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Barlin, Meltem, Jenna Clements et Jason Held. « Nox4 regulates cancer cell plasticity influencing autophagy state of cells. » Free Radical Biology and Medicine 192 (novembre 2022) : 97–98. http://dx.doi.org/10.1016/j.freeradbiomed.2022.10.174.

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Faes, Camille, Erica M. Sparkenbaugh et Rafal Pawlinski. « Hypercoagulable state in sickle cell disease ». Clinical Hemorheology and Microcirculation 68, n^o 2-3 (28 mars 2018) : 301–18. http://dx.doi.org/10.3233/ch-189013.

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Oslopova, A. A., A. M. Karpov et V. N. Oslopov. « Cell membrane state in schizophrenic patients ». Neurology Bulletin XXXV, n^o 1-2 (20 avril 2003) : 29–34. http://dx.doi.org/10.17816/nb89662.

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When investigating 216 schizophrenic patients a significant difference has been revealed in oscillation amplitude in absolute values of Na+Li+ countertransport at a period of time (speed variability of Na+Li+ countertransport), and having value s equal to 73,5, though in healthy people and people with different somatic diseases (even with bipolar disturbance) this variability is 13,515,7. Na+Li+ countertransport variability had not been changed because of the therapy, being present at the same level in schizophrenic patients both in acute periods and in the periods of remission. Discovered 5-fold increase of cell membrane permeability in Na+Li+ countertransport is probably aspecific (pathognomonic) sigh of schizophrenia.

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Calvert, J. M., T. J. Manuccia et R. J. Nowak. « A Polymeric Solid‐State Electrochromic Cell ». Journal of The Electrochemical Society 133, n^o 5 (1 mai 1986) : 951–53. http://dx.doi.org/10.1149/1.2108772.

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VALEO, TOM. « The State of Stem Cell Research ». Neurology Now 5, n^o 1 (janvier 2009) : 34–35. http://dx.doi.org/10.1097/01.nnn.0000345705.05677.19.

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Bretherton, Ross, Darrian Bugg, Emily Olszewski et Jennifer Davis. « Regulators of cardiac fibroblast cell state ». Matrix Biology 91-92 (septembre 2020) : 117–35. http://dx.doi.org/10.1016/j.matbio.2020.04.002.

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Matteocci, F., S. Casaluci, S. Razza, A. Guidobaldi, T. M. Brown, A. Reale et A. Di Carlo. « Solid state dye solar cell modules ». Journal of Power Sources 246 (janvier 2014) : 361–64. http://dx.doi.org/10.1016/j.jpowsour.2013.07.104.

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Holden, C. « Bay State Passes Stem Cell Bill ». Science 308, n^o 5719 (8 avril 2005) : 179c. http://dx.doi.org/10.1126/science.308.5719.179c.

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Casanova, Jordi. « Stemness as a cell default state ». EMBO reports 13, n^o 5 (10 avril 2012) : 396–97. http://dx.doi.org/10.1038/embor.2012.47.

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Ivanovska, Irena L., et Dennis Discher. « Crosslinked Collagen Films Affect Cell State ». Biophysical Journal 98, n^o 3 (janvier 2010) : 731a. http://dx.doi.org/10.1016/j.bpj.2009.12.4009.

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Zahn, L. M. « Chromatin state and the single cell ». Science 348, n^o 6237 (21 mai 2015) : 876. http://dx.doi.org/10.1126/science.348.6237.876-m.

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Brackston, Rowan D., Eszter Lakatos et Michael P. H. Stumpf. « Transition state characteristics during cell differentiation ». PLOS Computational Biology 14, n^o 9 (20 septembre 2018) : e1006405. http://dx.doi.org/10.1371/journal.pcbi.1006405.

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Kotila, Taiwo R. « Sickle Cell Trait : A Benign State ? » Acta Haematologica 136, n^o 3 (2016) : 147–51. http://dx.doi.org/10.1159/000446526.

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Background: Sickle cell trait (SCT) is the heterozygous form of sickle cell disease and expectedly should be a benign state with no complications ascribed to it. There are numerous reports challenging its being a benign condition, though this is controversial. Methods and Results: A review of the results of the accompanying investigations done on some of the patients show that beta thalassemia may be responsible for many of the ascribed symptoms and complications. These patients may therefore have sickle cell beta thalassemia, a compound heterozygous form of sickle cell disease. Conclusion: It is important to screen for beta thalassemia using red cell indices and quantitation of the different hemoglobin fractions before attributing any symptoms to SCT. DNA analysis, though useful in ascertaining the presence of the sickle cell gene, is not sufficient. There is the need to exclude the presence of mutations for beta thalassemia, which often is geographical region-specific.

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Muckenhuber, Markus, Isabelle Seufert, Katharina Müller-Ott, Jan-Philipp Mallm, Lara C. Klett, Caroline Knotz, Jana Hechler, Nick Kepper, Fabian Erdel et Karsten Rippe. « Epigenetic signals that direct cell type–specific interferon beta response in mouse cells ». Life Science Alliance 6, n^o 4 (2 février 2023) : e202201823. http://dx.doi.org/10.26508/lsa.202201823.

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The antiviral response induced by type I interferon (IFN) via the JAK-STAT signaling cascade activates hundreds of IFN-stimulated genes (ISGs) across human and mouse tissues but varies between cell types. However, the links between the underlying epigenetic features and the ISG profile are not well understood. We mapped ISGs, binding sites of the STAT1 and STAT2 transcription factors, chromatin accessibility, and histone H3 lysine modification by acetylation (ac) and mono-/tri-methylation (me1, me3) in mouse embryonic stem cells and fibroblasts before and after IFNβ treatment. A large fraction of ISGs and STAT-binding sites was cell type specific with promoter binding of a STAT1/2 complex being a key driver of ISGs. Furthermore, STAT1/2 binding to putative enhancers induced ISGs as inferred from a chromatin co-accessibility analysis. STAT1/2 binding was dependent on the chromatin context and positively correlated with preexisting H3K4me1 and H3K27ac marks in an open chromatin state, whereas the presence of H3K27me3 had an inhibitory effect. Thus, chromatin features present before stimulation represent an additional regulatory layer for the cell type–specific antiviral response.

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Liu, Y., B. Li, T. L. Hu, T. Li, Y. Zhang, C. Zhang, M. Yu et al. « Increased Phosphatidylserine on Blood Cells in Oral Squamous Cell Carcinoma ». Journal of Dental Research 98, n^o 7 (12 avril 2019) : 763–71. http://dx.doi.org/10.1177/0022034519843106.

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The specific function of phosphatidylserine (PS) in the context of the development of a hypercoagulable state among individuals with oral squamous cell carcinoma (OSCC) is uncertain. The goal of this study was therefore to assess the exposure of PS on microparticles (MPs) as well as on endothelial and blood cells and to assess procoagulant activity (PCA) as a function of the stage of OSCC progression. We recruited patients with OSCC ( n = 63) as well as healthy controls ( n = 26) to participate in this study. PS exposure was then assessed via confocal microscopy and flow cytometry, revealing that patients with stage III/IV OSCC exhibited higher frequencies of PS-exposing blood cells, MPs, and serum-cultured endothelial cells (ECs) than did patients with stage I/II OSCC or healthy controls. When we conducted functional coagulation assays, we discovered that PS+blood cells, MPs, and serum-cultured ECs from patients with stage III/IV OSCC mediated more rapid coagulation and more substantial production of FXa, thrombin, and fibrin as compared with controls. When samples were treated with the PS antagonist lactadherin, this resulted in an 80% disruption of PCA. Strikingly, when pre- and postoperative samples were compared from patients with stage III/IV OSCC undergoing resective surgery, PCA was significantly reduced in the postoperative samples. After stimulating ECs with inflammatory cytokines, we found by confocal microscopy that they expose PS on their cell membranes, thus generating FVa and FXa binding sites and mediating the formation of fibrin. Together our findings provide evidence that PS+blood cells and MPs are important mediators of the development of a hypercoagulable and prothrombotic state among individuals afflicted by advanced-stage OSCC. As such, a PS blockade may be a viable therapeutic strategy for treating such patients.

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Passegue, Emmanuelle, Amy J. Wagers, Sylvie Giuriato, Wade C. Anderson et Irving L. Weissman. « Cell Cycle Regulation and Cell Fate Decisions in Hematopoietic Stem Cells. » Blood 106, n^o 11 (16 novembre 2005) : 1349. http://dx.doi.org/10.1182/blood.v106.11.1349.1349.

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Abstract The blood is a perpetually renewing tissue seeded by a rare population of adult bone marrow hematopoietic stem cells (HSC). During steady-state hematopoiesis, the HSC population is relatively quiescent but constantly maintains a low numbers of cycling cells that differentiate to produce the various lineage of mature blood cells. However, in response to hematological stress, the entire HSC population can be recruited into cycle to self-renew and regenerate the blood-forming system. HSC proliferation is therefore highly adaptative and requires appropriate regulation of cell cycle progression to drive both differentiation-associated and self-renewal-associated proliferation, without depletion of the stem cell pool. Although the molecular events controlling HSC proliferation are still poorly understood, they are likely determined, at least in part, by regulated expression and/or function of components and regulators of the cell cycle machinery. Here, we demonstrate that the long-term self-renewing HSC (defined as Lin−/c-Kit+/Sca-1+/Thy1.1int/Flk2−) exists in two distinct states that are both equally important for their in vivo functions as stem cells: a numerically dominant quiescent state, which is critical for HSC function in hematopoietic reconstitution; and a proliferative state, which represents almost a fourth of this population and is essential for HSC functions in differentiation and self-renewal. We show that when HSC exit quiescence and enter G1 as a prelude to cell division, at least two critical events occur: first, during the G1 and subsequent S-G2/M phases, they temporarily lose efficient in vivo engraftment activity, while retaining in vitro differentiation potential; and second, they select the particular cell cycle proteins that are associated with specific developmental outcomes (self-renewal vs. differentiation) and developmental fates (myeloid vs. lymphoid). Together, these findings provide a direct link between HSC proliferation, cell cycle regulation and cell fate decisions that have critical implications for both the therapeutic use of HSC and the understanding of leukemic transformation.

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