scholarly journals Capicua regulates neural stem cell proliferation and lineage specification through control of Ets factors

2018 ◽  
Author(s):  
Shiekh Tanveer Ahmad ◽  
Alexandra D. Rogers ◽  
Myra J. Chen ◽  
Rajiv Dixit ◽  
Lata Adnani ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Cell Fate ◽  
Lineage Specification ◽  
Self Renewal ◽  
Important Regulator ◽  
Neuronal Lineage ◽  
Glial Lineage ◽  
Ets Factors ◽  
The Brain

ABSTRACTCapicua (Cic) is a transcriptional repressor mutated in the brain cancer oligodendroglioma. Despite its cancer link, little is known of Cic’s function in the brain. Here, we investigated the relationship between Cic expression and cell type specification in the brain. Cic is strongly expressed in astrocytic and neuronal lineage cells but is more weakly expressed in stem cells and oligodendroglial lineage cells. Using a new conditionalCicknockout mouse, we show that forebrain-specificCicdeletion increases proliferation and self-renewal of neural stem cells. Furthermore,Cicloss biases neural stem cells toward glial lineage selection, expanding the pool of oligodendrocyte precursor cells (OPCs). These proliferation and lineage selection effects in the developing brain are dependent on de-repression of Ets transcription factors. In patient-derived oligodendroglioma cells, CIC re-expression or ETV5 blockade decreases lineage bias, proliferation, self-renewal and tumorigenicity. Our results identify Cic is an important regulator of cell fate in neurodevelopment and oligodendroglioma, and suggest that its loss contributes to oligodendroglioma by promoting proliferation and an OPC-like identity via Ets overactivity.

scholarly journals Multiple layers of molecular controls modulate self-renewal and neuronal lineage specification of embryonic stem cells

2008 ◽  
Vol 17 (R1) ◽  
pp. R67-R75 ◽  
Author(s):  
G. W. Yeo ◽  
N. Coufal ◽  
S. Aigner ◽  
B. Winner ◽  
J. A. Scolnick ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Lineage Specification ◽  
Self Renewal ◽  
Neuronal Lineage

Neuroinflammation and physical exercise as modulators of adult hippocampal neural precursor cell behavior

2017 ◽  
Vol 29 (1) ◽  
pp. 1-20 ◽  
Author(s):  
Martha Pérez-Domínguez ◽  
Luis B. Tovar-y-Romo ◽  
Angélica Zepeda
Keyword(s):  
Stem Cells ◽  
Physical Exercise ◽  
Neural Stem Cells ◽  
Cell Fate ◽  
Bone Morphogenetic Proteins ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Adult Neural Stem Cells ◽  
Neurogenic Niche ◽  
Glial Lineage

Abstract The dentate gyrus of the hippocampus is a plastic structure where adult neurogenesis constitutively occurs. Cell components of the neurogenic niche are source of paracrine as well as membrane-bound factors such as Notch, Bone Morphogenetic Proteins, Wnts, Sonic Hedgehog, cytokines, and growth factors that regulate adult hippocampal neurogenesis and cell fate decision. The integration and coordinated action of multiple extrinsic and intrinsic cues drive a continuous decision process: if adult neural stem cells remain quiescent or proliferate, if they take a neuronal or a glial lineage, and if new cells proliferate, undergo apoptotic death, or survive. The proper balance in the molecular milieu of this neurogenic niche leads to the production of neurons in a higher rate as that of astrocytes. But this rate changes in face of microenvironment modifications as those driven by physical exercise or with neuroinflammation. In this work, we first review the cellular and molecular components of the subgranular zone, focusing on the molecules, active signaling pathways and genetic programs that maintain quiescence, induce proliferation, or promote differentiation. We then summarize the evidence regarding the role of neuroinflammation and physical exercise in the modulation of adult hippocampal neurogenesis with emphasis on the activation of progression from adult neural stem cells to lineage-committed progenitors to their progeny mainly in murine models.

scholarly journals Coordinated control of self-renewal and differentiation of neural stem cells by Myc and the p19ARF–p53 pathway

2008 ◽  
Vol 183 (7) ◽  
pp. 1243-1257 ◽  
Author(s):  
Motoshi Nagao ◽  
Kenneth Campbell ◽  
Kevin Burns ◽  
Chia-Yi Kuan ◽  
Andreas Trumpp ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Cell Fate ◽  
Late Stage ◽  
Early Stage ◽  
Dependent Manner ◽  
Self Renewal ◽  
P53 Pathway ◽  
Glial Fate ◽  
Underlying Mechanisms

The modes of proliferation and differentiation of neural stem cells (NSCs) are coordinately controlled during development, but the underlying mechanisms remain largely unknown. In this study, we show that the protooncoprotein Myc and the tumor suppressor p19ARF regulate both NSC self-renewal and their neuronal and glial fate in a developmental stage–dependent manner. Early-stage NSCs have low p19ARF expression and retain a high self-renewal and neurogenic capacity, whereas late-stage NSCs with higher p19ARF expression possess a lower self-renewal capacity and predominantly generate glia. Overexpression of Myc or inactivation of p19ARF reverts the properties of late-stage NSCs to those of early-stage cells. Conversely, inactivation of Myc or forced p19ARF expression attenuates self-renewal and induces precocious gliogenesis through modulation of the responsiveness to gliogenic signals. These actions of p19ARF in NSCs are mainly mediated by p53. We propose that opposing actions of Myc and the p19ARF–p53 pathway have important functions in coordinated developmental control of self-renewal and cell fate choices in NSCs.

scholarly journals Hypoxia induces early neurogenesis in human fetal neural stem cells by activating the WNT pathway.

2021 ◽  
Author(s):  
Devanjan Dey ◽  
Diksha Joshi ◽  
Vadanya Shrivastava ◽  
Chitra Mohinder Singh Singal ◽  
Sagar Tyagi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Wnt Signaling ◽  
Cell Fate ◽  
Ventricular Zone ◽  
Wnt Signaling Pathway ◽  
Lineage Commitment ◽  
Differentiation Potential ◽  
Hypoxia Exposure ◽  
Glial Lineage

Fetal neural stem cells (FNSCs) are present in the brain of human fetuses that differentiate into cells of neuronal and glial lineages. Difference in oxygen concentration between maternal and fetal circulation indicates that the developing fetus may be exposed to lower oxygen concentrations compared to adults. This physiological hypoxia may influence the growth and differentiation of the FNSCs. This study aimed to evaluate the effect of hypoxia on the differentiation potential of human FNSCs isolated from the sub-ventricular zone of aborted fetal brains (n=5). FNSCs were isolated, expanded, and characterized by Nestin and Sox2 expression, using immunocytochemistry and flowcytometry respectively. These FNSCs were exposed to 20% oxygen (normoxia) and 0.2% oxygen (hypoxia) concentrations for 48 hours, and hypoxia exposure (n=5) was evaluated by a panel of markers (CA9, PGK1 and VEGF). Whole human genome transcriptomic analyses (Genespring GX13) of FNSCs exposed to hypoxia (Agilent 4x44K human array slides), highlighted that genes associated with neurogenesis were getting enriched. The pathway analysis of these enriched genes (using Metacore) showed that WNT signaling played a role in determining the cell fate of FNSCs exposed to hypoxic environment. Microarray analyses was validated using neuronal and glial lineage commitment markers such as Ngn1, Ngn2, ASCL1, DCX, GFAP, Olig2 and Nkx2.2 using qPCR (n=9). This demonstrated upregulation of the neuronal commitment markers on hypoxia exposure, while no change was observed in astrocytic and oligodendrocyte lineage commitment markers. Increased expression of downstream targets of the WNT signaling pathway, TCF4 and ID2, by qPCR (n=9), indicated its involvement in mediating neuronal differentiation on exposure to hypoxia.

Mitochondrial dynamics in postmitotic cells regulate neurogenesis

Science ◽  
2020 ◽  
Vol 369 (6505) ◽  
pp. 858-862 ◽  
Author(s):  
Ryohei Iwata ◽  
Pierre Casimir ◽  
Pierre Vanderhaeghen
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Cell Fate ◽  
Time Window ◽  
Mitochondrial Dynamics ◽  
Human Cells ◽  
Self Renewal ◽  
Cortical Neurogenesis ◽  
Daughter Cells ◽  
Neuronal Fate

The conversion of neural stem cells into neurons is associated with the remodeling of organelles, but whether and how this is causally linked to fate change is poorly understood. We examined and manipulated mitochondrial dynamics during mouse and human cortical neurogenesis. We reveal that shortly after cortical stem cells have divided, daughter cells destined to self-renew undergo mitochondrial fusion, whereas those that retain high levels of mitochondria fission become neurons. Increased mitochondria fission promotes neuronal fate, whereas induction of mitochondria fusion after mitosis redirects daughter cells toward self-renewal. This occurs during a restricted time window that is doubled in human cells, in line with their increased self-renewal capacity. Our data reveal a postmitotic period of fate plasticity in which mitochondrial dynamics are linked with cell fate.

scholarly journals EphB4 Regulates Self-Renewal, Proliferation and Neuronal Differentiation of Human Embryonic Neural Stem Cells in Vitro

2017 ◽  
Vol 41 (2) ◽  
pp. 819-834 ◽  
Author(s):  
Tingting Liu ◽  
Xianwei Zeng ◽  
Fangling Sun ◽  
Hongli Hou ◽  
Yunqian Guan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Neuronal Differentiation ◽  
Glial Cells ◽  
Tyrosine Kinases ◽  
Fine Tuning ◽  
Brain Diseases ◽  
Self Renewal ◽  
Neuronal Lineage

Background/Aims: EphB4 belongs to the largest family of Eph receptor tyrosine kinases. It contributes to a variety of pathological progresses of cancer malignancy. However, little is known about its role in neural stem cells (NSCs). This study examined whether EphB4 is required for proliferation and differentiation of human embryonic neural stem cells (hNSCs) in vitro. Methods: We up- and down-regulated EphB4 expression in hNSCs using lentiviral over-expression and shRNA knockdown constructs and then investigated the influence of EphB4 on the properties of hNSCs. Results: Our results show that shRNA-mediated EphB4 reduction profoundly impaired hNSCs self-renewal and proliferation. Furthermore, detection of differentiation revealed that knockdown of EphB4 inhibited hNSCs differentiation towards a neuronal lineage and promoted hNSCs differentiation to glial cells. In contrast, EphB4 overexpression promoted hNSCs self-renewal and proliferation, further induced hNSCs differentiation towards a neuronal lineage and inhibited hNSCs differentiation to glial cells. Moreover, we found that EphB4 regulates cell proliferation mediated by the Abl-CyclinD1 pathway. Conclusion: These studies provide strong evidence that fine tuning of EphB4 expression is crucial for the proliferation and neuronal differentiation of hNSCs, suggesting that EphB4 might be an interesting target for overcoming some of the therapeutic limitations of neuronal loss in brain diseases.

Sign in / Sign up

Export Citation Format

Share Document