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Niche stiffness underlies the ageing of central nervous system progenitor cells | Nature
> We identify the mechanoresponsive ion channel PIEZO1 as a key mediator of OPC mechanical signalling. Inhibiting PIEZO1 overrides mechanical signals in vivo and allows OPCs to maintain activity in the ageing CNS. We also show that PIEZO1 is important in regulating cell number during CNS development.
aging  OPC  stiffness  stem_cells 
4 days ago by porejide
CD24 regulates stemness and the epithelial to mesenchymal transition through modulation of Notch1 mRNA stability by p38MAPK - ScienceDirect
example of how cd24 goes up with notch!

We report here that CD24 knockdown resulted in decreased expression of Notch1 in MCF-7 cells. CD24-downstream p38MAPK was shown to regulate Notch1 at the level of mRNA stability. We also found that CD24-mediated cell migration, invasion, mammosphere formation, and drug resistance was regulated by its downstream target Notch1. Together, our results indicate that CD24 may regulate the epithelial to mesenchymal transition and stemness through Notch1 signaling in breast cancer cells.
CD24  Notch  MCF7  stem_cells  EMT 
6 weeks ago by Segalllab
Cytokines, breast cancer stem cells (BCSCs) and chemoresistance | Clinical and Translational Medicine | Full Text
Interesting speculation about the role of aldh.

RA produced from aldehyde oxidation catalyzed by ALDH can bind to the nuclear retinoic acid receptors (RARs) or retinoid X receptors (RXRs). The heterodimer formed by RARs and RXRs recognizes a direct repeat of a 6 base pair DNA sequence motif with a 2 or 5 base pair spacer at the promoter region of many retinoid-inducible genes [101, 102]. In addition, RXR also can bind to DNA and regulate gene expression and cell differentiation as a homodimer [101]. ALDH can regulate gene expression through RAR signaling pathway, explaining the reason why ALDH plays an important role in the survival and differentiation of BCSCs (Fig. 3). Furthermore, the reprogramming of ALDH on genes expression profiling related to drug effects (genes involved in ABC transporter, DNA damage repair, clearance of reactive oxygen species) also explains the effect of ALDH+ BCSC on chemotherapeutic resistance [103].
aldh  stem_cells  chemoresistance  cytokines 
7 weeks ago by Segalllab
Upregulated SCUBE2 expression in breast cancer stem cells enhances triple negative breast cancer aggression through modulation of notch signaling and epithelial-to-mesenchymal transition - ScienceDirect
Interesting but disturbing that they seem to show 231 cells with Ecadherin, and also do not described their cd44/24 flow isolation although I think they have to have done this....

Background

Metastatic and/or recurrent breast carcinomas are leading causes of cancer-related death worldwide. Breast cancer stem cells (BCSCs) have been implicated in cancer metastases and progression, thus, the need for the discovery and development of effective BCSCs-specific therapies against metastatic and triple negative breast cancer (TNBC). The expression of SCUBE2, originally identified in vascular endothelia, then in several non-endothelial cell types, is downregulated in invasive breast carcinomas. However, the role of SCUBE2 in BCSCs remains unknown. This present study investigated the probable involvements of SCUBE2 in BCSCs and TNBC metastasis.
Methods

The mRNA expression of SCUBE2, stemness and EMT markers in MDA-MB-231 and Hs578T tumorspheres or adherent cells were evaluated by qRT-PCR and microarray analyses. Using gene overexpression, in vitro migration and invasion assays, as well as in vivo bioluminescence imaging, we evaluated the role of SCUBE2 in MDA-MB-231 or Hs578T BCSCs. Western blot and cytotoxicity assays helped identify and validate SCUBE2 molecular target(s) and inhibitor(s).
Results

Concurrently increased SCUBE2 expression and cell motility were observed in TNBC tumorspheres compared to the parental adherent cells. SCUBE2 overexpression augmented BCSCs motility in vitro, and enhanced TNBC metastasis in vivo. While SCUBE2 overexpression activated Notch signaling its downregulation suppressed Notch signal effectors NICD, Jagged 1, HEY1, and HES1.
Conclusions

We demonstrate that SCUBE2 expression is upregulated in BCSCs, promote EMT and enhance TNBC metastasis by activating Notch signaling. This reveals a potential druggable molecular target and an effective therapeutic strategy against metastatic and aggressive TNBC.
231_cells  stem_cells  mammosphere 
8 weeks ago by Segalllab
Genome-Wide RNAi Screen Identifies PMPCB as a Therapeutic Vulnerability in EpCAM+ Hepatocellular Carcinoma | Cancer Research
hcc, but indicates a link between mitochondria and EpCAM as a stemlike marker

Hepatocellular carcinoma (HCC) is a genetically heterogeneous disease for which a dominant actionable molecular driver has not been identified. Patients with the stem cell–like EpCAM+AFP+ HCC subtype have poor prognosis. Here, we performed a genome-wide RNAi screen to identify genes with a synthetic lethal interaction with EpCAM as a potential therapeutic target for the EpCAM+AFP+ HCC subtype. We identified 26 candidate genes linked to EpCAM/Wnt/β-catenin signaling and HCC cell growth. We further characterized the top candidate PMPCB, which plays a role in mitochondrial protein processing, as a bona fide target for EpCAM+ HCC. PMPCB blockage suppressed EpCAM expression and Wnt/β-catenin signaling via mitochondria-related reactive oxygen species production and FOXO activities, resulting in apoptosis and tumor suppression. These results indicate that a synthetic lethality screen is a viable strategy to identify actionable drivers of HCC and identify PMPCB as a therapeutically vulnerable gene in EpCAM+ HCC subpopulations.

Significance: This study identifies PMPCB as critical to mitochondrial homeostasis and a synthetic lethal candidate that selectively kills highly resistant EpCAM+ HCC tumors by inactivating the Wnt/β-catenin signaling pathway.
epcam  mitochondria  stem_cells 
9 weeks ago by Segalllab
CD44+/CD24− breast cancer cells exhibit phenotypic reversion in three-dimensional self-assembling peptide RADA16 nanofiber scaffold
Compare cd44/cd24 of 231, mcf10a, bt549 and 435 cells - 549 has high cd24....mostly worked with 435 for some reason...


Background

Self-assembling peptide nanofiber scaffolds have been shown to be a permissive biological material for tissue repair, cell proliferation, differentiation, etc. Recently, a subpopulation (CD44+/CD24−) of breast cancer cells has been reported to have stem/progenitor cell properties. The aim of this study was to investigate whether this subpopulation of cancer cells have different phenotypes in self-assembling COCH3-RADARADARADARADA-CONH2 (RADA16) peptide nanofiber scaffold compared with Matrigel® (BD Biosciences, Two Oak Park, Bedford, MA, USA) and collagen I.
Methods

CD44 and CD24 expression was determined by flow cytometry. Cell proliferation was measured by 5-bromo-2′-deoxyuridine assay and DNA content measurement. Immunostaining was used to indicate the morphologies of cells in three-dimensional (3D) cultures of different scaffolds and the localization of β-catenin in the colonies. Western blot was used to determine the expression of signaling proteins. In vitro migration assay and inoculation into nude mice were used to evaluate invasion and tumorigenesis in vivo.
Results

The breast cancer cell line MDA-MB-435S contained a high percentage (>99%) of CD44+/CD24− cells, which exhibited phenotypic reversion in 3D RADA16 nanofiber scaffold compared with collagen I and Matrigel. The newly formed reverted acini-like colonies reassembled a basement membrane and reorganized their cytoskeletons. At the same time, cells cultured and embedded in RADA16 peptide scaffold exhibited growth arrest. Also, they exhibited different migration potential, which links their migration ability with their cellular morphology. Consistent with studies in vitro, the in vivo tumor formation assay further supported of the functional changes caused by the reversion in 3D RADA16 culture. Expression levels of intercellular surface adhesion molecule-1 were upregulated in cells cultured in RADA16 scaffolds, and the NF-kappa B inhibitor pyrrolidine dithiocarbamate could inhibit RADA16-induced upregulation of intercellular surface adhesion molecule-1 and the phenotype reversion of MDA-MB-453S cells.
Conclusion

Culturing a CD44+/CD24−-enriched breast cancer cell population in 3D RADA16 peptide nanofiber scaffold led to a significant phenotypic reversion compared with Matrigel and collagen I.
stem_cells  CD44  CD24  231_cells  BT549  MCF10A 
10 weeks ago by Segalllab
Single-Cell Transcriptomes Distinguish Stem Cell State Changes and Lineage Specification Programs in Early Mammary Gland Development: Cell Reports
sc rnaseq of mammary gland devleopment in mouse
The mammary gland consists of cells with gene expression patterns reflecting their cellular origins, function, and spatiotemporal context. However, knowledge of developmental kinetics and mechanisms of lineage specification is lacking. We address this significant knowledge gap by generating a single-cell transcriptome atlas encompassing embryonic, postnatal, and adult mouse mammary development. From these data, we map the chronology of transcriptionally and epigenetically distinct cell states and distinguish fetal mammary stem cells (fMaSCs) from their precursors and progeny. fMaSCs show balanced co-expression of factors associated with discrete adult lineages and a metabolic gene signature that subsides during maturation but reemerges in some human breast cancers and metastases. These data provide a useful resource for illuminating mammary cell heterogeneity, the kinetics of differentiation, and developmental correlates of tumorigenesis.
scRNAseq  mammary_development  stem_cells 
may 2019 by Segalllab
Breast cancer stem cells: Features, key drivers and treatment options - ScienceDirect
very interesting review - should think about wnt on TNTs

Detailed analysis of the CD44+/CD24−/low and ALDEFLOUR-positive subpopulations revealed that CD44+/CD24−/low-BCSCs display a mesenchymal and ALDEFLOUR-positive BCSCs an epithelial phenotype and that BCSCs can reversibly transit between these two states [44], processes called EMT (epithelial-to-mesenchymal transition) and MET (mesenchymal-to-epithelial transition) (see Section 2.2.). The mesenchymal BCSCs (EMT-BCSCs) were found to be more invasive, but quiescent, whereas the epithelial BCSCs (MET-BCSCs) are less invasive, but mitotically active. The bipotent ALDEFLOUR-positive CD44+/CD24−/low –BCSC is supposedly the transit form between these two states [45]. It has been suggested that differentiated epithelial breast cancer cells emerge from epithelial BCSCs and differentiated mesenchymal cells from mesenchymal BCSCs [46]. This may explain why luminal breast cancer with a higher proportion of ALDEFLOUR-positive MET-BCSCs show an epithelial-like phenotype, whereas claudin-low breast cancer with a higher proportion of CD44+/CD24−/low EMT-BCSCs display a mesenchymal phenotype [45].
breast_cancer  stem_cells  Notch  wnt  chemotherapy 
april 2019 by Segalllab
LSECtin on tumor-associated macrophages enhances breast cancer stemness via interaction with its receptor BTN3A3 | Cell Research
Possible mediator of TNT/exosome induction of stemness

Macrophages have been suggested to contribute to constructing a cancer stem cell (CSC) niche. However, whether and how macrophages regulate the activity of CSCs through juxtacrine signaling are poorly understood. Here we report LSECtin, a transmembrane protein highly expressed on tumor-associated macrophages (TAMs), enhances stemness of breast cancer cells (BCCs). We identified BTN3A3, a B7 family member with previously unknown functions as the receptor for LSECtin on BCCs responsible for stemness-promoting effect of LSECtin. In mice bearing human tumor xenografts, either macrophage-specific ablation of LSECtin or silencing of BTN3A3 in BCCs decreased CSC frequency and tumor growth. Admixture of LSECtin-positive macrophages increased the tumorigenic activity of BCCs dependent on BTN3A3. Disruption of the LSECtin-BTN3A3 axis with BTN3A3-Fc or anti-BTN3A3 mAb has a therapeutic effect on breast cancer. These findings define a juxtacrine signaling mechanism by which TAMs promote cancer stemness. Targeting this axis in the CSC niche may provide potential therapies to breast cancer.
231_cells  cancer_stem_cells  stem_cells  TNTs  exosomes  drug_resistance  chemoresistance 
april 2019 by Segalllab
IJMS | Free Full-Text | Crosstalk between Notch, HIF-1α and GPER in Breast Cancer EMT | HTML
hypoxia may synergize with notch to induce emt/stemness? Maybe GPx2 can substitute?

The Notch signaling pathway acts in both physiological and pathological conditions, including embryonic development and tumorigenesis. In cancer progression, diverse mechanisms are involved in Notch-mediated biological responses, including angiogenesis and epithelial-mesenchymal-transition (EMT). During EMT, the activation of cellular programs facilitated by transcriptional repressors results in epithelial cells losing their differentiated features, like cell–cell adhesion and apical–basal polarity, whereas they gain motility. As it concerns cancer epithelial cells, EMT may be consequent to the evolution of genetic/epigenetic instability, or triggered by factors that can act within the tumor microenvironment. Following a description of the Notch signaling pathway and its major regulatory nodes, we focus on studies that have given insights into the functional interaction between Notch signaling and either hypoxia or estrogen in breast cancer cells, with a particular focus on EMT. Furthermore, we describe the role of hypoxia signaling in breast cancer cells and discuss recent evidence regarding a functional interaction between HIF-1α and GPER in both breast cancer cells and cancer-associated fibroblasts (CAFs). On the basis of these studies, we propose that a functional network between HIF-1α, GPER and Notch may integrate tumor microenvironmental cues to induce robust EMT in cancer cells. Further investigations are required in order to better understand how hypoxia and estrogen signaling may converge on Notch-mediated EMT within the context of the stroma and tumor cells interaction. However, the data discussed here may anticipate the potential benefits of further pharmacological strategies targeting breast cancer progression.
Notch  hypoxia  stem_cells  ROS  hif1alpha 
march 2019 by Segalllab
Upregulated SCUBE2 expression in breast cancer stem cells enhances triple negative breast cancer aggression through modulation of notch signaling and epithelial-to-mesenchymal transition - ScienceDirect
Possibly interesting - SCUBE2 overexpression in 231 cells increases notch, oct4 and stemness. Does not help that their previous paper said it acted as a tumor suppressor...

Metastatic and/or recurrent breast carcinomas are leading causes of cancer-related death worldwide. Breast cancer stem cells (BCSCs) have been implicated in cancer metastases and progression, thus, the need for the discovery and development of effective BCSCs-specific therapies against metastatic and triple negative breast cancer (TNBC). The expression of SCUBE2, originally identified in vascular endothelia, then in several non-endothelial cell types, is downregulated in invasive breast carcinomas. However, the role of SCUBE2 in BCSCs remains unknown. This present study investigated the probable involvements of SCUBE2 in BCSCs and TNBC metastasis.
Methods

The mRNA expression of SCUBE2, stemness and EMT markers in MDA-MB-231 and Hs578T tumorspheres or adherent cells were evaluated by qRT-PCR and microarray analyses. Using gene overexpression, in vitro migration and invasion assays, as well as in vivo bioluminescence imaging, we evaluated the role of SCUBE2 in MDA-MB-231 or Hs578T BCSCs. Western blot and cytotoxicity assays helped identify and validate SCUBE2 molecular target(s) and inhibitor(s).
Results

Concurrently increased SCUBE2 expression and cell motility were observed in TNBC tumorspheres compared to the parental adherent cells. SCUBE2 overexpression augmented BCSCs motility in vitro, and enhanced TNBC metastasis in vivo. While SCUBE2 overexpression activated Notch signaling its downregulation suppressed Notch signal effectors NICD, Jagged 1, HEY1, and HES1.
Conclusions

We demonstrate that SCUBE2 expression is upregulated in BCSCs, promote EMT and enhance TNBC metastasis by activating Notch signaling. This reveals a potential druggable molecular target and an effective therapeutic strategy against metastatic and aggressive TNBC.
Notch  231_cells  stem_cells 
march 2019 by Segalllab
Targeting Breast Cancer Stem Cell State Equilibrium through Modulation of Redox Signaling - ScienceDirect
Although breast cancer stem cells (BCSCs) display plasticity transitioning between quiescent mesenchymal-like (M) and proliferative epithelial-like (E) states, how this plasticity is regulated by metabolic or oxidative stress remains poorly understood. Here, we show that M- and E-BCSCs rely on distinct metabolic pathways and display markedly different sensitivities to inhibitors of glycolysis and redox metabolism. Metabolic or oxidative stress generated by 2DG, H2O2, or hypoxia promotes the transition of ROSlo M-BCSCs to a ROShi E-state. This transition is reversed by N-acetylcysteine and mediated by activation of the AMPK-HIF1α axis. Moreover, E-BCSCs exhibit robust NRF2-mediated antioxidant responses, rendering them vulnerable to ROS-induced differentiation and cytotoxicity following suppression of NRF2 or downstream thioredoxin (TXN) and glutathione (GSH) antioxidant pathways. Co-inhibition of glycolysis and TXN and GSH pathways suppresses tumor growth, tumor-initiating potential, and metastasis by eliminating both M- and E-BCSCs. Exploiting metabolic vulnerabilities of distinct BCSC states provides a novel therapeutic approach targeting this critical tumor cell population.
oxidative_stress  h202  ROS  stem_cells  EMT 
march 2019 by Segalllab
Cross‐Tissue Identification of Somatic Stem and Progenitor Cells Using a Single‐Cell RNA‐Sequencing Derived Gene Signature - Schwalie - 2017 - STEM CELLS - Wiley Online Library
LCP1 may drive stemness? Possible mir375 connection to stemness?

A long‐standing question in biology is whether multipotent somatic stem and progenitor cells (SSPCs) feature molecular properties that could guide their system‐independent identification. Population‐based transcriptomic studies have so far not been able to provide a definite answer, given the rarity and heterogeneous nature of these cells. Here, we exploited the resolving power of single‐cell RNA‐sequencing to develop a computational model that is able to accurately distinguish SSPCs from differentiated cells across tissues. The resulting classifier is based on the combined expression of 23 genes including known players in multipotency, proliferation, and tumorigenesis, as well as novel ones, such as Lcp1 and Vgll4 that we functionally validate in intestinal organoids. We show how this approach enables the identification of stem‐like cells in still ambiguous systems such as the pancreas and the epidermis as well as the exploration of lineage commitment hierarchies, thus facilitating the study of biological processes such as cellular differentiation, tissue regeneration, and cancer. Stem Cells 2017;35:2390–2402
lcp1  stem_cells  miR-375 
february 2019 by Segalllab
Differential Up-regulation of MAP Kinase Phosphatases MKP3/DUSP6 and DUSP5 by Ets2 and c-Jun Converge in the Control of the Growth Arrest Versus Proliferation Response of MCF-7 Breast Cancer Cells to Phorbol Ester
Mainly studies with MCF7 but indicate that DUSP6/MKP3 can induce motility(?stemness?) together with growth arrest.


Different levels of regulation account for the inactivation of MAP kinases by MAPK phosphatases (MKPs), in a cell type- and stimuli-dependent manner. MCF-7 human breast carcinoma cells treated with the phorbol 12-myristate 13-acetate (PMA) suffer growth arrest and show morphological alterations, which depend on the activation of the ERK1/2 MAP kinases. MKP3/DUSP6 and DUSP5 MAP kinase phosphatases, two negative regulators of ERK1/2, were specifically up-regulated in MCF-7 and SKBR3 cells in response to PMA. MKP3 and DUSP5 up-regulation required the prolonged activation of the ERK1/2 pathway, and correlated with the shutdown of this route. MKP3 induction relied on the activation of the Ets2 transcription factor, whereas DUSP5 induction depended on the activation of c-Jun. Diminishing the expression of MKP3 and DUSP5 raised the activation of ERK1/2, and accelerated growth arrest of PMA-treated MCF-7 cells. Conversely, MCF-7 cell lines expressing high levels of MKP3 or DUSP5 did not undergo PMA-triggered growth arrest, displayed a migratory phenotype, and formed colonies in soft agar. We propose that the differential up-regulation of MKP3 by Ets2 and of DUSP5 by c-Jun may converge in similar functional roles for these MAP kinase phosphatases in the growth arrest versus proliferation decisions of breast cancer cells.
dusp6  stem_cells  migration  growth_arrest 
february 2019 by Segalllab
Telomerase reverse transcriptase coordinates with the epithelial-to-mesenchymal transition through a feedback loop to define properties of breast cancer stem cells | Biology Open
All done with 231 cells. interesting that hTERT expression correlates with mesenchymal and stem characteristics

Telomerase and its core component, telomerase reverse transcriptase (hTERT), are critical for stem cell compartment integrity. Normal adult stem cells have the longest telomeres in a given tissue, a property mediated by high hTERT expression and high telomerase enzymatic activity. In contrast, cancer stem cells (CSCs) have short telomeres despite high expression of hTERT, indicating that the role of hTERT in CSCs is not limited to telomere elongation and/or maintenance. The function of hTERT in CSCs remains poorly understood. Here, we knocked down hTERT expression in CSCs and observed a morphological shift to a more epithelial phenotype, suggesting a role for hTERT in the epithelial-to-mesenchymal transition (EMT) of CSCs. Therefore, in this study, we systematically explored the relationship between hTERT and EMT and identified a reciprocal, bi-directional feedback loop between hTERT and EMT in CSCs. We found that hTERT expression is mutually exclusive to the mesenchymal phenotype and that, reciprocally, loss of the mesenchymal phenotype represses hTERT expression. We also showed that hTERT plays a critical role in the expression of key CSC markers and nuclear β-catenin localization, increases the percentage of cells with side-population properties, and upregulates the CD133 expression. hTERT also promotes chemoresistance properties, tumorsphere formation and other important functional CSC properties. Subsequently, hTERT knockdown leads to the loss of the above advantages, indicating a loss of CSC properties. Our findings suggest that targeting hTERT might improve CSCs elimination by transitioning them from the aggressive mesenchymal state to a more steady epithelial state, thereby preventing cancer progression.
231_cells  EMT  mesenchymal_motion  stem_cells  hTERT 
february 2019 by Segalllab
Two to Tango: Dialog between Immunity and Stem Cells in Health and Disease - ScienceDirect
Discussion of macrophages and contributions to stemness - mention notch activation of macrophages to make wnts in mammary gland


Stem cells in mammary glands (MaSCs) also require signals from tissue macrophages for ductal morphogenesis (Gyorki et al., 2009). Chakrabarti and colleagues discovered that MaSCs express a Notch ligand Delta like 1 (DLL1), which activates resident Notch-expressing macrophages (Chakrabarti et al., 2018). This interaction stimulates macrophages to produce Wnt ligands, which in turn triggers MaSC proliferation.
stem_cells  Macrophages  Notch  delta_ligands 
february 2019 by Segalllab
Inhibition of HER2 Increases JAGGED1-dependent Breast Cancer Stem Cells: Role for Membrane JAGGED1 | Clinical Cancer Research
Look at HER2 positive cells, and note that inhibition leads to exposure of intracellular JAG1 to the cell surface. Also have a TMA stain for JAG1 .

Purpose: HER2-positive breast cancer is driven by cells possessing stem-like properties of self-renewal and differentiation, referred to as cancer stem cells (CSC). CSCs are implicated in radiotherapy, chemotherapy resistance, and tumor recurrence. NOTCH promotes breast CSC survival and self-renewal, and overexpression of NOTCH1 and the NOTCH ligand JAGGED1 predict poor outcome. Resistance to anti-HER2 therapy in HER2+ breast cancer requires NOTCH1, and that combination of trastuzumab and a gamma secretase inhibitor (GSI) prevents tumor relapse in xenograft models.

Experimental Design: The current study investigates mechanisms by which HER2 tyrosine kinase activity regulates NOTCH-dependent CSC survival and tumor initiation.

Results: Lapatinib-mediated HER2 inhibition shifts the population of HER2+ breast cancer cells from low membrane JAGGED1 expression to higher levels, independent of sensitivity to anti-HER2 treatment within the bulk cell population. This increase in membrane JAGGED1 is associated with higher NOTCH receptor expression, activation, and enrichment of CSCs in vitro and in vivo. Importantly, lapatinib treatment results in growth arrest and cell death of JAGGED1 low-expressing cells while the JAGGED1 high-expressing cells continue to cycle. High membrane JAGGED1 protein expression predicts poor overall cumulative survival in women with HER2+ breast cancer.

Conclusions: These results indicate that higher membrane JAGGED1 expression may be used to either predict response to anti-HER2 therapy or for detection of NOTCH-sensitive CSCs posttherapy. Sequential blockade of HER2 followed by JAGGED1 or NOTCH could be more effective than simultaneous blockade to prevent drug resistance and tumor progression. Clin Cancer Res; 24(18); 4566–78. ©2018 AACR.
JAG1  ErbB2  Her2  intracellular_location  stem_cells  aldefluor  cancer_stem_cells 
february 2019 by Segalllab
Stem Cells Remember Tissues’ Past Injuries | Quanta Magazine
Stem cells seem to retain memories of old injuries to improve future healing. When that system goes wrong, chronic inflammation can result.
articles  stem_cells 
november 2018 by gmisra
Single-Cell Transcriptomics and Fate Mapping of Ependymal Cells Reveals an Absence of Neural Stem Cell Function - ScienceDirect
Just what the title says...flow effects presumably are on neighboring cells.


"Highlights



High-fidelity genetic labeling and analysis of ependymal cells in the adult V-SVZ


Ependymal cells are transcriptionally distinct from neural stem cells


Ependymal cells express cilia genes (e.g., FoxJ1), not angiogenic genes (e.g., Flt1)


Ependymal cells don’t behave as neural stem cells or progenitors in vitro or in vivo

Summary

Ependymal cells are multi-ciliated cells that form the brain’s ventricular epithelium and a niche for neural stem cells (NSCs) in the ventricular-subventricular zone (V-SVZ). In addition, ependymal cells are suggested to be latent NSCs with a capacity to acquire neurogenic function. This remains highly controversial due to a lack of prospective in vivo labeling techniques that can effectively distinguish ependymal cells from neighboring V-SVZ NSCs. We describe a transgenic system that allows for targeted labeling of ependymal cells within the V-SVZ. Single-cell RNA-seq revealed that ependymal cells are enriched for cilia-related genes and share several stem-cell-associated genes with neural stem or progenitors. Under in vivo and in vitro neural-stem- or progenitor-stimulating environments, ependymal cells failed to demonstrate any suggestion of latent neural-stem-cell function. These findings suggest remarkable stability of ependymal cell function and provide fundamental insights into the molecular signature of the V-SVZ niche.
ependyma  cilia  stem_cells 
october 2018 by Segalllab

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