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1

Xing, Liujing, Teni Anbarchian, Jonathan M. Tsai, Giles W. Plant, and Roeland Nusse. "Wnt/β-catenin signaling regulates ependymal cell development and adult homeostasis." Proceedings of the National Academy of Sciences 115, no. 26 (June 11, 2018): E5954—E5962. http://dx.doi.org/10.1073/pnas.1803297115.

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In the adult mouse spinal cord, the ependymal cell population that surrounds the central canal is thought to be a promising source of quiescent stem cells to treat spinal cord injury. Relatively little is known about the cellular origin of ependymal cells during spinal cord development, or the molecular mechanisms that regulate ependymal cells during adult homeostasis. Using genetic lineage tracing based on the Wnt target geneAxin2, we have characterized Wnt-responsive cells during spinal cord development. Our results revealed that Wnt-responsive progenitor cells are restricted to the dorsal midline throughout spinal cord development, which gives rise to dorsal ependymal cells in a spatially restricted pattern. This is contrary to previous reports that suggested an exclusively ventral origin of ependymal cells, suggesting that ependymal cells may retain positional identities in relation to their neural progenitors. Our results further demonstrated that in the postnatal and adult spinal cord, all ependymal cells express the Wnt/β-catenin signaling target geneAxin2, as well as Wnt ligands. Genetic elimination of β-catenin or inhibition of Wnt secretion in Axin2-expressing ependymal cells in vivo both resulted in impaired proliferation, indicating that Wnt/β-catenin signaling promotes ependymal cell proliferation. These results demonstrate the continued importance of Wnt/β-catenin signaling for both ependymal cell formation and regulation. By uncovering the molecular signals underlying the formation and regulation of spinal cord ependymal cells, our findings thus enable further targeting and manipulation of this promising source of quiescent stem cells for therapeutic interventions.
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Mothe, Andrea J., Iris Kulbatski, Rita L. van Bendegem, Linda Lee, Eiji Kobayashi, Armand Keating, and Charles H. Tator. "Analysis of Green Fluorescent Protein Expression in Transgenic Rats for Tracking Transplanted Neural Stem/Progenitor Cells." Journal of Histochemistry & Cytochemistry 53, no. 10 (June 27, 2005): 1215–26. http://dx.doi.org/10.1369/jhc.5a6639.2005.

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Green fluorescent protein (GFP) expression was evaluated in tissues of different transgenic rodents—Sprague-Dawley (SD) rat strain [SD-Tg(GFP)Bal], W rat strain [Wistar-TgN(CAG-GFP)184ys], and M mouse strain [Tg(GFPU)5Nagy/J]—by direct fluorescence of native GFP expression and by immunohistochemistry. The constitutively expressing GFP transgenic strains showed tissue-specific differences in GFP expression, and GFP immunohistochemistry amplified the fluorescent signal. The fluorescence of stem/progenitor cells cultured as neurospheres from the ependymal region of the adult spinal cord from the GFP SD and W rat strains was assessed in vitro. After transplantation of the cells into wildtype spinal cord, the ability to track the grafted cells was evaluated in vivo. Cultured stem/progenitor cells from the SD strain required GFP immunostaining to be visualized. Likewise, after transplantation of SD cells into the spinal cord, immunohistochemical amplification of the GFP signal was required for detection. In contrast, GFP expression of stem/progenitor cells generated from the W strain was readily detected by direct fluorescence both in vitro and in vivo without the need for immunohistochemical amplification. The cultured stem/progenitor cells transplanted into the spinal cord survived for at least 49 days after transplantation, and continued to express GFP, demonstrating stable expression of the GFP transgene in vivo.
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Rodriguez-Jimenez, Francisco, Ana Alastrue-Agudo, Miodrag Stojkovic, Slaven Erceg, and Victoria Moreno-Manzano. "Connexin 50 Expression in Ependymal Stem Progenitor Cells after Spinal Cord Injury Activation." International Journal of Molecular Sciences 16, no. 11 (November 6, 2015): 26608–18. http://dx.doi.org/10.3390/ijms161125981.

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4

Rodriguez-Jimenez, Francisco Javier, Ana Alastrue, Miodrag Stojkovic, Slaven Erceg, and Victoria Moreno-Manzano. "Connexin 50 modulates Sox2 expression in spinal-cord-derived ependymal stem/progenitor cells." Cell and Tissue Research 365, no. 2 (May 24, 2016): 295–307. http://dx.doi.org/10.1007/s00441-016-2421-y.

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5

Finkel, Zachary, Fatima Esteban, Brianna Rodriguez, Tianyue Fu, Xin Ai, and Li Cai. "Diversity of Adult Neural Stem and Progenitor Cells in Physiology and Disease." Cells 10, no. 8 (August 10, 2021): 2045. http://dx.doi.org/10.3390/cells10082045.

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Adult neural stem and progenitor cells (NSPCs) contribute to learning, memory, maintenance of homeostasis, energy metabolism and many other essential processes. They are highly heterogeneous populations that require input from a regionally distinct microenvironment including a mix of neurons, oligodendrocytes, astrocytes, ependymal cells, NG2+ glia, vasculature, cerebrospinal fluid (CSF), and others. The diversity of NSPCs is present in all three major parts of the CNS, i.e., the brain, spinal cord, and retina. Intrinsic and extrinsic signals, e.g., neurotrophic and growth factors, master transcription factors, and mechanical properties of the extracellular matrix (ECM), collectively regulate activities and characteristics of NSPCs: quiescence/survival, proliferation, migration, differentiation, and integration. This review discusses the heterogeneous NSPC populations in the normal physiology and highlights their potentials and roles in injured/diseased states for regenerative medicine.
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6

Gotoh, Yukiko. "IL2 Neural stem cell regulation and brain development." Neuro-Oncology Advances 3, Supplement_6 (December 1, 2021): vi1. http://dx.doi.org/10.1093/noajnl/vdab159.001.

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Abstract Quiescent neural stem cells (NSCs) in the adult mouse brain are the source of neurogenesis that regulates innate and adaptive behaviors. Adult NSCs in the subventricular zone (SVZ) are derived from a subpopulation of embryonic neural stem-progenitor cells (NPCs) that is characterized by a slower cell cycle relative to the more abundant rapid cycling NPCs that build the brain. We have previously shown that slow cell cycle can cause the establishment of adult NSCs at the SVZ, although the underlying mechanism remains unknown. We found that Notch and an effector Hey1 form a module that is upregulated by cell cycle arrest in slowly dividing NPCs. In contrast to the oscillatory expression of the Notch effectors Hes1 and Hes5 in fast cycling progenitors, Hey1 displays a non-oscillatory stationary expression pattern and contributes to the long-term maintenance of NSCs. These findings reveal a novel division of labor in Notch effectors where cell cycle rate biases effector selection and cell fate. I will also discuss the heterogeneity of slowly dividing embryonic NPCs and the lineage relationship between adult NSCs and ependymal cells, which together form the niche for adult neurogenesis at the SVZ.
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7

Donato, Sarah V., and Matthew K. Vickaryous. "Radial Glia and Neuronal-like Ependymal Cells Are Present within the Spinal Cord of the Trunk (Body) in the Leopard Gecko (Eublepharis macularius)." Journal of Developmental Biology 10, no. 2 (June 1, 2022): 21. http://dx.doi.org/10.3390/jdb10020021.

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As is the case for many lizards, leopard geckos (Eublepharis macularius) can self-detach a portion of their tail to escape predation, and then regenerate a replacement complete with a spinal cord. Previous research has shown that endogenous populations of neural stem/progenitor cells (NSPCs) reside within the spinal cord of the original tail. In response to tail loss, these NSPCs are activated and contribute to regeneration. Here, we investigate whether similar populations of NSPCs are found within the spinal cord of the trunk (body). Using a long-duration 5-bromo-2′-deoxyuridine pulse-chase experiment, we determined that a population of cells within the ependymal layer are label-retaining following a 20-week chase. Tail loss does not significantly alter rates of ependymal cell proliferation within the trunk spinal cord. Ependymal cells of the trunk spinal cord express SOX2 and represent at least two distinct cell populations: radial glial-like (glial fibrillary acidic protein- and Vimentin-expressing) cells; and neuronal-like (HuCD-expressing) cells. Taken together, these data demonstrate that NSPCs of the trunk spinal cord closely resemble those of the tail and support the use of the tail spinal cord as a less invasive proxy for body spinal cord injury investigations.
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8

Marcuzzo, Stefania, Dimos Kapetis, Renato Mantegazza, Fulvio Baggi, Silvia Bonanno, Claudia Barzago, Paola Cavalcante, Nicole Kerlero de Rosbo, and Pia Bernasconi. "Altered miRNA expression is associated with neuronal fate in G93A-SOD1 ependymal stem progenitor cells." Experimental Neurology 253 (March 2014): 91–101. http://dx.doi.org/10.1016/j.expneurol.2013.12.007.

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9

Redmond, Stephanie A., María Figueres-Oñate, Kirsten Obernier, Marcos Assis Nascimento, Jose I. Parraguez, Laura López-Mascaraque, Luis C. Fuentealba, and Arturo Alvarez-Buylla. "Development of Ependymal and Postnatal Neural Stem Cells and Their Origin from a Common Embryonic Progenitor." Cell Reports 27, no. 2 (April 2019): 429–41. http://dx.doi.org/10.1016/j.celrep.2019.01.088.

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10

Mokhtar, Doaa M., Ramy K. A. Sayed, Giacomo Zaccone, Marco Albano, and Manal T. Hussein. "Ependymal and Neural Stem Cells of Adult Molly Fish (Poecilia sphenops, Valenciennes, 1846) Brain: Histomorphometry, Immunohistochemical, and Ultrastructural Studies." Cells 11, no. 17 (August 27, 2022): 2659. http://dx.doi.org/10.3390/cells11172659.

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This study was conducted on 16 adult specimens of molly fish (Poecilia sphenops) to investigate ependymal cells (ECs) and their role in neurogenesis using ultrastructural examination and immunohistochemistry. The ECs lined the ventral and lateral surfaces of the optic ventricle and their processes extended through the tectal laminae and ended at the surface of the tectum as a subpial end-foot. Two cell types of ECs were identified: cuboidal non-ciliated (5.68 ± 0.84/100 μm2) and columnar ciliated (EC3.22 ± 0.71/100 μm2). Immunohistochemical analysis revealed two types of GFAP immunoreactive cells: ECs and astrocytes. The ECs showed the expression of IL-1β, APG5, and Nfr2. Moreover, ECs showed immunostaining for myostatin, S100, and SOX9 in their cytoplasmic processes. The proliferative activity of the neighboring stem cells was also distinct. The most interesting finding in this study was the glia–neuron interaction, where the processes of ECs met the progenitor neuronal cells in the ependymal area of the ventricular wall. These cells showed bundles of intermediate filaments in their processes and basal poles and were connected by desmosomes, followed by gap junctions. Many membrane-bounded vesicles could be demonstrated on the surface of the ciliated ECs that contained neurosecretion. The abluminal and lateral cell surfaces of ECs showed pinocytotic activities with many coated vesicles, while their apical cytoplasm contained centrioles. The occurrence of stem cells in close position to the ECs, and the presence of bundles of generating axons in direct contact with these stem cells indicate the role of ECs in neurogenesis. The TEM results revealed the presence of neural stem cells in a close position to the ECs, in addition to the presence of bundles of generating axons in direct contact with these stem cells. The present study indicates the role of ECs in neurogenesis.
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11

Park, Sang In, Jung Yeon Lim, Chang Hyun Jeong, Seong Muk Kim, Jin Ae Jun, Sin-Soo Jeun, and Won Il Oh. "Human Umbilical Cord Blood-Derived Mesenchymal Stem Cell Therapy Promotes Functional Recovery of Contused Rat Spinal Cord through Enhancement of Endogenous Cell Proliferation and Oligogenesis." Journal of Biomedicine and Biotechnology 2012 (2012): 1–8. http://dx.doi.org/10.1155/2012/362473.

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Numerous studies have shown the benefits of mesenchymal stem cells (MSCs) on the repair of spinal cord injury (SCI) model and on behavioral improvement, but the underlying mechanisms remain unclear. In this study, to investigate possible mechanisms by which MSCs contribute to the alleviation of neurologic deficits, we examined the potential effect of human umbilical cord blood-derived MSCs (hUCB-MSCs) on the endogenous cell proliferation and oligogenesis after SCI. SCI was injured by contusion using a weight-drop impactor and hUCB-MSCs were transplanted into the boundary zone of the injured site. Animals received a daily injection of bromodeoxyuridine (BrdU) for 7 days after treatment to identity newly synthesized cells of ependymal and periependymal cells that immunohistochemically resembled stem/progenitor cells was evident. Behavior analysis revealed that locomotor functions of hUCB-MSCs group were restored significantly and the cavity volume was smaller in the MSCs-transplanted rats compared to the control group. In MSCs-transplanted group, TUNEL-positive cells were decreased and BrdU-positive cells were significantly increased rats compared with control group. In addition, more of BrdU-positive cells expressed neural stem/progenitor cell nestin and oligo-lineage cell such as NG2, CNPase, MBP and glial fibrillary acidic protein typical of astrocytes in the MSC-transplanted rats. Thus, endogenous cell proliferation and oligogenesis contribute to MSC-promoted functional recovery following SCI.
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12

Donson, Andrew, Austin Gillen, Riemondy Kent, Ahmed Gilani, Sujatha Venkataraman, Bridget Sanford, Andrea Griesinger, et al. "EPEN-31. SINGLE-CELL RNAseq OF CHILDHOOD EPENDYMOMA REVEALS DISTINCT NEOPLASTIC CELL SUBPOPULATIONS THAT IMPACT ETIOLOGY, MOLECULAR CLASSIFICATION AND OUTCOME." Neuro-Oncology 22, Supplement_3 (December 1, 2020): iii314. http://dx.doi.org/10.1093/neuonc/noaa222.167.

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Abstract Ependymoma (EPN) is a brain tumor commonly presenting in childhood that remains fatal in the majority of children. Intra-tumoral cellular heterogeneity in bulk-tumor samples significantly confounds our understanding of EPN biology, impeding development of effective therapy. We therefore used single-cell RNA sequencing to catalog cellular heterogeneity of 26 childhood EPN, predominantly from ST-RELA, PFA1 and PFA2 subgroups. ST-RELA and PFA subgroups clustered separately, with ST-RELA clustering largely according to individual sample-of-origin. PFA1 and PFA2 subgroup EPNs cells were intermixed and revealed 4 major subpopulations – 2 with characteristics of ependymal differentiation (transporter and ciliated phenotype subpopulations), an undifferentiated subpopulation and a mesenchymal phenotype. Pseudotime analysis showed the undifferentiated progenitor subpopulation either differentiating into ependymal differentiation subpopulations or transitioning into the mesenchymal subpopulation. Histological analysis revealed that undifferentiated and mesenchymal subpopulations cells colocalized to perinecrotic/perivascular zones, the putative ependymoma stem cell niche. Deconvolution of PFA bulk transcriptome data showed that undifferentiated and mesenchymal subpopulations were associated with a poor prognosis; whereas the ciliated ependymal cell-differentiated subpopulation was associated with a good prognosis. In conflict with current distinct classification paradigms, the ratio of mesenchymal and ciliated subpopulations determined bulk-tumor subgroups assignment to PFA1 and PFA2 respectively. This atlas of EPN cellular heterogeneity provides an important advance in our understanding of EPN biology, identifying high-risk associated subpopulations for therapeutic targeting.
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13

Mitra, Siddhartha S., Abdullah H. Feroze, Sharareh Gholamin, Chase Richard, Rogelio Esparza, Michael Zhang, Tej D. Azad, et al. "Neural Placode Tissue Derived From Myelomeningocele Repair Serves as a Viable Source of Oligodendrocyte Progenitor Cells." Neurosurgery 77, no. 5 (July 29, 2015): 794–802. http://dx.doi.org/10.1227/neu.0000000000000918.

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Abstract BACKGROUND: The presence, characteristics, and potential clinical relevance of neural progenitor populations within the neural placodes of myelomeningocele patients remain to be studied. Neural stem cells are known to reside adjacent to ependyma-lined surfaces along the central nervous system axis. OBJECTIVE: Given such neuroanatomic correlation and regenerative capacity in fetal development, we assessed myelomeningocele-derived neural placode tissue as a potentially novel source of neural stem and progenitor cells. METHODS: Nonfunctional neural placode tissue was harvested from infants during the surgical repair of myelomeningocele and subsequently further analyzed by in vitro studies, flow cytometry, and immunofluorescence. To assess lineage potential, neural placode-derived neurospheres were subjected to differential media conditions. Through assessment of platelet-derived growth factor receptor α (PDGFRα) and CD15 cell marker expression, Sox2+Olig2+ putative oligodendrocyte progenitor cells were successfully isolated. RESULTS: PDGFRαhiCD15hi cell populations demonstrated the highest rate of self-renewal capacity and multipotency of cell progeny. Immunofluorescence of neural placode-derived neurospheres demonstrated preferential expression of the oligodendrocyte progenitor marker, CNPase, whereas differentiation to neurons and astrocytes was also noted, albeit to a limited degree. CONCLUSION: Neural placode tissue contains multipotent progenitors that are preferentially biased toward oligodendrocyte progenitor cell differentiation and presents a novel source of such cells for use in the treatment of a variety of pediatric and adult neurological disease, including spinal cord injury, multiple sclerosis, and metabolic leukoencephalopathies.
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Marcuzzo, Stefania, Davide Isaia, Silvia Bonanno, Claudia Malacarne, Paola Cavalcante, Antonella Zacheo, Valentino Laquintana, et al. "FM19G11-Loaded Gold Nanoparticles Enhance the Proliferation and Self-Renewal of Ependymal Stem Progenitor Cells Derived from ALS Mice." Cells 8, no. 3 (March 23, 2019): 279. http://dx.doi.org/10.3390/cells8030279.

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Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting motor neurons. In ALS mice, neurodegeneration is associated with the proliferative restorative attempts of ependymal stem progenitor cells (epSPCs) that normally lie in a quiescent in the spinal cord. Thus, modulation of the proliferation of epSPCs may represent a potential strategy to counteract neurodegeneration. Recent studies demonstrated that FM19G11, a hypoxia-inducible factor modulator, induces epSPC self-renewal and proliferation. The aim of the study was to investigate whether FM19G11-loaded gold nanoparticles (NPs) can affect self-renewal and proliferation processes in epSPCs isolated from G93A-SOD1 mice at disease onset. We discovered elevated levels of SOX2, OCT4, AKT1, and AKT3, key genes associated with pluripotency, self-renewal, and proliferation, in G93A-SOD1 epSPCs at the transcriptional and protein levels after treatment with FM19G11-loaded NPs. We also observed an increase in the levels of the mitochondrial uncoupling protein (UCP) gene in treated cells. FM19G11-loaded NPs treatment also affected the expression of the cell cycle-related microRNA (miR)-19a, along with its target gene PTEN, in G93A-SOD1 epSPCs. Overall our findings establish the significant impact of FM19G11-loaded NPs on the cellular pathways involved in self-renewal and proliferation in G93A-SOD1 epSPCs, thus providing an impetus to the design of novel tailored approaches to delay ALS disease progression.
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Shinozuka, Takuma, and Shinji Takada. "Morphological and Functional Changes of Roof Plate Cells in Spinal Cord Development." Journal of Developmental Biology 9, no. 3 (July 30, 2021): 30. http://dx.doi.org/10.3390/jdb9030030.

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The most dorsal region, or roof plate, is the dorsal organizing center of developing spinal cord. This region is also involved in development of neural crest cells, which are the source of migratory neural crest cells. During early development of the spinal cord, roof plate cells secrete signaling molecules, such as Wnt and BMP family proteins, which regulate development of neural crest cells and dorsal spinal cord. After the dorso-ventral pattern is established, spinal cord dynamically changes its morphology. With this morphological transformation, the lumen of the spinal cord gradually shrinks to form the central canal, a cavity filled with cerebrospinal fluid that is connected to the ventricular system of the brain. The dorsal half of the spinal cord is separated by a glial structure called the dorsal (or posterior) median septum. However, underlying mechanisms of such morphological transformation are just beginning to be understood. Recent studies reveal that roof plate cells dramatically stretch along the dorso-ventral axis, accompanied by reduction of the spinal cord lumen. During this stretching process, the tips of roof plate cells maintain contact with cells surrounding the shrinking lumen, eventually exposed to the inner surface of the central canal. Interestingly, Wnt expression remains in stretched roof plate cells and activates Wnt/β-catenin signaling in ependymal cells surrounding the central canal. Wnt/β-catenin signaling in ependymal cells promotes proliferation of neural progenitor and stem cells in embryonic and adult spinal cord. In this review, we focus on the role of the roof plate, especially that of Wnt ligands secreted by roof plate cells, in morphological changes occurring in the spinal cord.
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Mothe, A. J., and C. H. Tator. "Proliferation, migration, and differentiation of endogenous ependymal region stem/progenitor cells following minimal spinal cord injury in the adult rat." Neuroscience 131, no. 1 (January 2005): 177–87. http://dx.doi.org/10.1016/j.neuroscience.2004.10.011.

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McDonough, Ashley, and Verónica Martínez-Cerdeño. "Endogenous Proliferation after Spinal Cord Injury in Animal Models." Stem Cells International 2012 (2012): 1–16. http://dx.doi.org/10.1155/2012/387513.

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Spinal cord injury (SCI) results in motor and sensory deficits, the severity of which depends on the level and extent of the injury. Animal models for SCI research include transection, contusion, and compression mouse models. In this paper we will discuss the endogenous stem cell response to SCI in animal models. All SCI animal models experience a similar peak of cell proliferation three days after injury; however, each specific type of injury promotes a specific and distinct stem cell response. For example, the transection model results in a strong and localized initial increase of proliferation, while in contusion and compression models, the initial level of proliferation is lower but encompasses the entire rostrocaudal extent of the spinal cord. All injury types result in an increased ependymal proliferation, but only in contusion and compression models is there a significant level of proliferation in the lateral regions of the spinal cord. Finally, the fate of newly generated cells varies from a mainly oligodendrocyte fate in contusion and compression to a mostly astrocyte fate in the transection model. Here we will discuss the potential of endogenous stem/progenitor cell manipulation as a therapeutic tool to treat SCI.
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18

Gómez-Villafuertes, Rosa, Francisco Javier Rodríguez-Jiménez, Ana Alastrue-Agudo, Miodrag Stojkovic, María Teresa Miras-Portugal, and Victoria Moreno-Manzano. "Purinergic Receptors in Spinal Cord-Derived Ependymal Stem/Progenitor Cells and Their Potential Role in Cell-Based Therapy for Spinal Cord Injury." Cell Transplantation 24, no. 8 (August 2015): 1493–509. http://dx.doi.org/10.3727/096368914x682828.

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19

Horiguchi, Kotaro, Saishu Yoshida, Rumi Hasegawa, Shu Takigami, Shunji Ohsako, Takako Kato, and Yukio Kato. "Isolation and characterization of cluster of differentiation 9-positive ependymal cells as potential adult neural stem/progenitor cells in the third ventricle of adult rats." Cell and Tissue Research 379, no. 3 (December 2, 2019): 497–509. http://dx.doi.org/10.1007/s00441-019-03132-5.

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Wittmann, Gabor, Surbhi Gahlot, Malcolm James Low, and Ronald M. Lechan. "Rax Expression Identifies a Novel Cell Type in the Adult Mouse Hypothalamus." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A42. http://dx.doi.org/10.1210/jendso/bvab048.082.

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Abstract Hypothalamic tanycytes are radial glia-like ependymal cells lining the ventrolateral walls and floor of the third ventricle. Recent data show that tanycytes are adult neural stem/progenitor cells, capable of generating neurons that populate the adjacent hypothalamic nuclei involved in the regulation of feeding and energy balance. Thus, the genetic fate mapping of tanycytes has become an invaluable tool to identify and study tanycyte-derived adult-born hypothalamic neurons. Perhaps the most selective tanycyte marker identified to date is the retina and anterior neural fold homeobox (Rax), that has been used as a tanycyte marker in multiple single-cell transcriptomic studies. By using in situ hybridization and immunofluorescence, we show that Rax mRNA and RAX protein are also expressed in a minor but significant population of parenchymal cells that are concentrated in the caudal arcuate nucleus. RAX-positive nuclei in the parenchyma were often observed in pairs, suggesting recent cell divisions. The morphology of these cells was studied in tamoxifen-treated Rax-CreERT2; Ai34(RCL-Syp/tdT)-D mice, in which the synaptophysin-tdTomato fusion protein permanently labels Rax-expressing cells and their progeny. While some parenchymal RAX-positive cells had tanycyte-like morphology indicative of tanycyte migration into the parenchyma, the majority had a very different morphology with extensive local processes that often encircled adjacent neurons (termed “frizzy cells”). The tdTomato labeling also revealed numerous frizzy cells that were negative for RAX, indicating downregulation of endogenous Rax expression subsequent to the induction of synaptophysin-tdTomato reporter expression. Many of these cells were distributed outside the caudal arcuate nucleus, including the rostral lateral arcuate nucleus, ventromedial and dorsomedial hypothalamic nuclei and lateral hypothalamus. RAX-negative frizzy cells were also conspicuous in the paraventricular nucleus, and occasionally observed in the preoptic region and bed nucleus of the stria terminalis. Frizzy cells were negative for the tanycyte-enriched proteins vimentin, monocarboxylate transporter 8 (MCT8) or glial fibrillary acidic protein (GFAP). These results identify a novel Rax-expressing cell type in the adult hypothalamus that differs from tanycytes in location, morphology and gene expression characteristics. Future studies are required to determine whether frizzy cells are derived from tanycytes or constitute a separate cell lineage, and whether they represent a migratory form of neural precursor cells in the adult hypothalamus.
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Henzi, Roberto, Montserrat Guerra, Karin Vío, César González, Cristian Herrera, Pat McAllister, Conrad Johanson, and Esteban M. Rodríguez. "Neurospheres from neural stem/neural progenitor cells (NSPCs) of non-hydrocephalic HTx rats produce neurons, astrocytes and multiciliated ependyma: the cerebrospinal fluid of normal and hydrocephalic rats supports such a differentiation." Cell and Tissue Research 373, no. 2 (April 12, 2018): 421–38. http://dx.doi.org/10.1007/s00441-018-2828-8.

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Ribeiro, Ana, Joana F. Monteiro, Ana C. Certal, Ana M. Cristovão, and Leonor Saúde. "Foxj1a is expressed in ependymal precursors, controls central canal position and is activated in new ependymal cells during regeneration in zebrafish." Open Biology 7, no. 11 (November 2017): 170139. http://dx.doi.org/10.1098/rsob.170139.

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Zebrafish are able to regenerate the spinal cord and recover motor and sensory functions upon severe injury, through the activation of cells located at the ependymal canal. Here, we show that cells surrounding the ependymal canal in the adult zebrafish spinal cord express Foxj1a. We demonstrate that ependymal cells express Foxj1a from their birth in the embryonic neural tube and that Foxj1a activity is required for the final positioning of the ependymal canal. We also show that in response to spinal cord injury, Foxj1a ependymal cells actively proliferate and contribute to the restoration of the spinal cord structure. Finally, this study reveals that Foxj1a expression in the injured spinal cord is regulated by regulatory elements activated during regeneration. These data establish Foxj1a as a pan-ependymal marker in development, homeostasis and regeneration and may help identify the signals that enable this progenitor population to replace lost cells after spinal cord injury.
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Itokazu, Yutaka, Masaaki Kitada, Mari Dezawa, Akira Mizoguchi, Naoya Matsumoto, Akira Shimizu, and Chizuka Ide. "Choroid plexus ependymal cells host neural progenitor cells in the rat." Glia 53, no. 1 (2005): 32–42. http://dx.doi.org/10.1002/glia.20255.

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YÜKSEL, Hasan, and Emre ZAFER. "Endometrial Stem/Progenitor Cells." Current Obstetrics and Gynecology Reports 9, no. 1 (February 29, 2020): 7–14. http://dx.doi.org/10.1007/s13669-020-00278-w.

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Maruyama, Tetsuo. "Endometrial stem/progenitor cells." Journal of Obstetrics and Gynaecology Research 40, no. 9 (August 27, 2014): 2015–22. http://dx.doi.org/10.1111/jog.12501.

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26

Rao, Shilpa, Niveditha Ravindra, Nishanth Sadashiva, Bhagavatula Indira Devi, and Vani Santosh. "Anaplastic Ependymoma With Ganglionic Differentiation: Report of a Rare Case and Implications in Diagnosis." International Journal of Surgical Pathology 25, no. 7 (May 29, 2017): 644–47. http://dx.doi.org/10.1177/1066896917710716.

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Ependymomas are glial neoplasms with rare cases exhibiting neuronal differentiation. We describe a case of spinal anaplastic ependymoma with ganglionic differentiation in a 28-year-old woman. The ganglionic component was labeled by synaptophysin, whereas the rest of the tumor showed features of an anaplastic ependymoma. Stem cell marker MELK was noted to stain both the neoplastic ependymal and ganglionic components, possibly suggesting a stem cell/progenitor origin for the tumor with subsequent divergent differentiation.
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Yoder, Mervin C. "Endothelial stem and progenitor cells (stem cells): (2017 Grover Conference Series)." Pulmonary Circulation 8, no. 1 (November 3, 2017): 204589321774395. http://dx.doi.org/10.1177/2045893217743950.

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The capacity of existing blood vessels to give rise to new blood vessels via endothelial cell sprouting is called angiogenesis and is a well-studied biologic process. In contrast, little is known about the mechanisms for endothelial cell replacement or regeneration within established blood vessels. Since clear definitions exist for identifying cells with stem and progenitor cell properties in many tissues and organs of the body, several groups have begun to accumulate evidence that endothelial stem and progenitor cells exist within the endothelial intima of existing blood vessels. This paper will review stem and progenitor cell definitions and highlight several recent papers purporting to have identified resident vascular endothelial stem and progenitor cells.
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Moreno-Manzano, Victoria, Francisco Javier Rodríguez-Jiménez, Mireia García-Roselló, Sergio Laínez, Slaven Erceg, Maria Teresa Calvo, Mohammad Ronaghi, et al. "Activated Spinal Cord Ependymal Stem Cells Rescue Neurological Function." Stem Cells 27, no. 3 (March 2009): 733–43. http://dx.doi.org/10.1002/stem.24.

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Wang, Xusehng. "Stem/Progenitor Cells in Skin." Journal of Stem Cells Research, Development & Therapy 5, no. 1 (September 25, 2019): 1–5. http://dx.doi.org/10.24966/srdt-2060/100016.

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Pittatore, G., A. Moggio, C. Benedetto, B. Bussolati, and A. Revelli. "Endometrial Adult/Progenitor Stem Cells." Reproductive Sciences 21, no. 3 (September 13, 2013): 296–304. http://dx.doi.org/10.1177/1933719113503405.

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31

Ardhanareeswaran, Karthikeyan, and Maria Mirotsou. "Lung Stem and Progenitor Cells." Respiration 85, no. 2 (2013): 89–95. http://dx.doi.org/10.1159/000346500.

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32

Fu, Hui, Yingchuan Qi, Min Tan, Jun Cai, Xuemei Hu, Zijing Liu, Jan Jensen, and Mengsheng Qiu. "Molecular mapping of the origin of postnatal spinal cord ependymal cells: Evidence that adult ependymal cells are derived from Nkx6.1+ ventral neural progenitor cells." Journal of Comparative Neurology 456, no. 3 (January 13, 2003): 237–44. http://dx.doi.org/10.1002/cne.10481.

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33

Zhao, Xiangshan, Gautam K. Malhotra, Hamid Band, and Vimla Band. "Derivation of Myoepithelial Progenitor Cells from Bipotent Mammary Stem/Progenitor Cells." PLoS ONE 7, no. 4 (April 13, 2012): e35338. http://dx.doi.org/10.1371/journal.pone.0035338.

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34

Sugimura, Ryohichi, Deepak Kumar Jha, Areum Han, Clara Soria-Valles, Edroaldo Lummertz da Rocha, Yi-Fen Lu, Jeremy A. Goettel, et al. "Haematopoietic stem and progenitor cells from human pluripotent stem cells." Nature 545, no. 7655 (May 17, 2017): 432–38. http://dx.doi.org/10.1038/nature22370.

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35

Bjerknes, Matthew, and Hazel Cheng. "Gastrointestinal Stem Cells. II. Intestinal stem cells." American Journal of Physiology-Gastrointestinal and Liver Physiology 289, no. 3 (September 2005): G381—G387. http://dx.doi.org/10.1152/ajpgi.00160.2005.

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Current views of the identity, distribution, and regulation of small intestinal epithelial stem cells and their immediate progeny are discussed. Recent works implicating Wnt signaling in stem and progenitor proliferation, the involvement of Notch signaling in epithelial lineage specification, and the role of hedgehog and bone morphogenetic protein families in crypt formation are integrated. We had the good fortune that many of these papers came in pairs from independent groups. We attempt to identify points of agreement, reinterpret each in the context of the other, and indicate directions for continued progress.
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36

Tesche, Leora J., and David A. Gerber. "Tissue-Derived Stem and Progenitor Cells." Stem Cells International 2010 (2010): 1–7. http://dx.doi.org/10.4061/2010/824876.

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The characterization and isolation of various stem cell populations, from embryonic through tissue-derived stem cells, have led a rapid growth in the field of stem cell research. These research efforts have often been interrelated as to the markers that identify a select cell population are frequently analyzed to determine their expression in cells of distinct organs/tissues. In this review, we will expand the current state of research involving select tissue-derived stem cell populations including the liver, central nervous system, and cardiac tissues as examples of the success and challenges in this field of research. Lastly, the challenges of clinical therapies will be discussed as it applies to these unique cell populations.
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37

Crane, Jennifer F., and Paul A. Trainor. "Neural Crest Stem and Progenitor Cells." Annual Review of Cell and Developmental Biology 22, no. 1 (November 2006): 267–86. http://dx.doi.org/10.1146/annurev.cellbio.22.010305.103814.

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38

Zhang, Li, and Qingbo Xu. "Stem/Progenitor Cells in Vascular Regeneration." Arteriosclerosis, Thrombosis, and Vascular Biology 34, no. 6 (June 2014): 1114–19. http://dx.doi.org/10.1161/atvbaha.114.303809.

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39

Rodolfo, Carlo, Sabrina Di Bartolomeo, and Francesco Cecconi. "Autophagy in stem and progenitor cells." Cellular and Molecular Life Sciences 73, no. 3 (October 26, 2015): 475–96. http://dx.doi.org/10.1007/s00018-015-2071-3.

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40

Lin, Yi-Hui, Yu-Chun Huang, Li-Hsin Chen, and Pei-Ming Chu. "Autophagy in cancer stem/progenitor cells." Cancer Chemotherapy and Pharmacology 75, no. 5 (November 26, 2014): 879–86. http://dx.doi.org/10.1007/s00280-014-2634-2.

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41

Ziegler, Benedikt L., and Lothar Kanz. "Expansion of stem and progenitor cells." Current Opinion in Hematology 5, no. 6 (November 1998): 434–40. http://dx.doi.org/10.1097/00062752-199811000-00014.

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42

Deane, James A., Rosa C. Gualano, and Caroline E. Gargett. "Regenerating endometrium from stem/progenitor cells." Current Opinion in Obstetrics and Gynecology 25, no. 3 (June 2013): 193–200. http://dx.doi.org/10.1097/gco.0b013e32836024e7.

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43

Kapur, Sahil K., Severiano Dos-Anjos Vilaboa, Ramon Llull, and Adam J. Katz. "Adipose Tissue and Stem/Progenitor Cells." Clinics in Plastic Surgery 42, no. 2 (April 2015): 155–67. http://dx.doi.org/10.1016/j.cps.2014.12.010.

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44

Itoh, Tohru, and Atsushi Miyajima. "Liver regeneration by stem/progenitor cells." Hepatology 59, no. 4 (February 14, 2014): 1617–26. http://dx.doi.org/10.1002/hep.26753.

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45

Hai-Jiang, Wu, Deng Xin-Na, and Duan Hui-Jun. "Expansion of hematopoietic stem/progenitor cells." American Journal of Hematology 83, no. 12 (December 2008): 922–26. http://dx.doi.org/10.1002/ajh.21262.

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46

Itoh, Tohru. "Stem/progenitor cells in liver regeneration." Hepatology 64, no. 2 (June 24, 2016): 663–68. http://dx.doi.org/10.1002/hep.28661.

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47

Pinto do Ó, Perpétua, Karin Richter, and Leif Carlsson. "Hematopoietic progenitor/stem cells immortalized byLhx2 generate functional hematopoietic cells in vivo." Blood 99, no. 11 (June 1, 2002): 3939–46. http://dx.doi.org/10.1182/blood.v99.11.3939.

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Hematopoietic stem cells (HSCs) are unique in their capacity to maintain blood formation following transplantation into immunocompromised hosts. Expansion of HSCs in vitro is therefore important for many clinical applications but has met with limited success because the mechanisms regulating the self-renewal process are poorly defined. We have previously shown that expression of the LIM-homeobox gene Lhx2 in hematopoietic progenitor cells derived from embryonic stem cells differentiated in vitro generates immortalized multipotent hematopoietic progenitor cell lines. However, HSCs of early embryonic origin, including those derived from differentiated embryonic stem cells, are inefficient in engrafting adult recipients upon transplantation. To address whetherLhx2 can immortalize hematopoietic progenitor/stem cells that can engraft adult recipients, we expressed Lhx2 in hematopoietic progenitor/stem cells derived from adult bone marrow. This approach allowed for the generation of immortalized growth factor–dependent hematopoietic progenitor/stem cell lines that can generate erythroid, myeloid, and lymphoid cells upon transplantation into lethally irradiated mice. When transplanted into stem cell–deficient mice, these cell lines can generate a significant proportion of circulating erythrocytes in primary, secondary, and tertiary recipients for at least 18 months. Thus, Lhx2immortalizes multipotent hematopoietic progenitor/stem cells that can generate functional progeny following transplantation into lethally irradiated hosts and can long-term repopulate stem cell–deficient hosts.
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48

Chevreau, Robert, Hussein Ghazale, Chantal Ripoll, Chaima Chalfouh, Quentin Delarue, Anne Laure Hemonnot-Girard, Daria Mamaeva, et al. "RNA Profiling of Mouse Ependymal Cells after Spinal Cord Injury Identifies the Oncostatin Pathway as a Potential Key Regulator of Spinal Cord Stem Cell Fate." Cells 10, no. 12 (November 27, 2021): 3332. http://dx.doi.org/10.3390/cells10123332.

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Ependymal cells reside in the adult spinal cord and display stem cell properties in vitro. They proliferate after spinal cord injury and produce neurons in lower vertebrates but predominantly astrocytes in mammals. The mechanisms underlying this glial-biased differentiation remain ill-defined. We addressed this issue by generating a molecular resource through RNA profiling of ependymal cells before and after injury. We found that these cells activate STAT3 and ERK/MAPK signaling post injury and downregulate cilia-associated genes and FOXJ1, a central transcription factor in ciliogenesis. Conversely, they upregulate 510 genes, seven of them more than 20-fold, namely Crym, Ecm1, Ifi202b, Nupr1, Rbp1, Thbs2 and Osmr—the receptor for oncostatin, a microglia-specific cytokine which too is strongly upregulated after injury. We studied the regulation and role of Osmr using neurospheres derived from the adult spinal cord. We found that oncostatin induced strong Osmr and p-STAT3 expression in these cells which is associated with reduction of proliferation and promotion of astrocytic versus oligodendrocytic differentiation. Microglial cells are apposed to ependymal cells in vivo and co-culture experiments showed that these cells upregulate Osmr in neurosphere cultures. Collectively, these results support the notion that microglial cells and Osmr/Oncostatin pathway may regulate the astrocytic fate of ependymal cells in spinal cord injury.
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49

Haller, Hermann, Kirsten De Groot, Ferdinand Bahlmann, Marlies Elger, and Danilo Fliser. "Stem cells and progenitor cells in renal disease." Kidney International 68, no. 5 (November 2005): 1932–36. http://dx.doi.org/10.1111/j.1523-1755.2005.00622.x.

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50

Wu, Min, and Yu-Quan Wei. "Development of Respiratory Stem Cells and Progenitor Cells." Stem Cells and Development 13, no. 6 (December 2004): 607–13. http://dx.doi.org/10.1089/scd.2004.13.607.

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