Specification and maintenance of oligodendrocyte precursor cells from neural progenitor cells: involvement of microRNA-7a

The generation of myelinating cells from multipotential neural stem cells in the CNS requires the initiation of specific gene expression programs in oligodendrocytes (OLs). We reasoned that microRNAs (miRNAs) could play an important role in this process by regulating genes crucial for OL development. Here we identified miR-7a as one of the highly enriched miRNAs in oligodendrocyte precursor cells (OPCs), overexpression of which in either neural progenitor cells (NPCs) or embryonic mouse cortex promoted the generation of OL lineage cells. Blocking the function of miR-7a in differentiating NPCs led to a reduction in OL number and an expansion of neuronal populations simultaneously. We also found that overexpression of this miRNA in purified OPC cultures promoted cell proliferation and inhibited further maturation. In addition, miR-7a might exert the effects just mentioned partially by directly repressing proneuronal differentiation factors including Pax6 and NeuroD4, or proOL genes involved in oligodendrocyte maturation. These results suggest that miRNA pathway is essential in determining cell fate commitment for OLs and thus providing a new strategy for modulating this process in OL loss diseases.

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Presenilin-1 regulates neuronal differentiation during neurogenesis

Development ◽

10.1242/dev.127.12.2593 ◽

2000 ◽

Vol 127 (12) ◽

pp. 2593-2606 ◽

Cited By ~ 1

Author(s):

M. Handler ◽

X. Yang ◽

J. Shen

Keyword(s):

Cell Death ◽

Progenitor Cells ◽

Neuronal Differentiation ◽

Cell Fate ◽

Neural Progenitor Cells ◽

Apoptotic Cell ◽

Ventricular Zone ◽

Neural Progenitor ◽

Apoptotic Cell Death ◽

Presenilin 1

Mutations in Presenilin-1 (PS1) are a major cause of familial Alzheimer's disease. Our previous studies showed that PS1 is required for murine neural development. Here we report that lack of PS1 leads to premature differentiation of neural progenitor cells, indicating a role for PS1 in a cell fate decision between postmitotic neurons and neural progenitor cells. Neural proliferation and apoptotic cell death during neurogenesis are unaltered in PS1(−/−) mice, suggesting that the reduction in the neural progenitor cells observed in the PS1(−/−) brain is due to premature differentiation of progenitor cells, rather than to increased apoptotic cell death or decreased cell proliferation. In addition, the premature neuronal differentiation in the PS1(−/−) brain is associated with aberrant neuronal migration and disorganization of the laminar architecture of the developing cerebral hemisphere. In the ventricular zone of PS1(−/−) mice, expression of the Notch1 downstream effector gene Hes5 is reduced and expression of the Notch1 ligand Dll1 is elevated, whereas expression of Notch1 is unchanged. The level of Dll1 transcripts is also increased in the presomitic mesoderm of PS1(−/−) embryos, while the level of Notch1 transcripts is unchanged, in contrast to a previous report (Wong et al., 1997, Nature 387, 288–292). These results provide direct evidence that PS1 controls neuronal differentiation in association with the downregulation of Notch signalling during neurogenesis.

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SEPT7 Interacts with KIF20A and Regulates the Proliferative State of Neural Progenitor Cells During Cortical Development

Cerebral Cortex ◽

10.1093/cercor/bhz292 ◽

2019 ◽

Vol 30 (5) ◽

pp. 3030-3043 ◽

Cited By ~ 2

Author(s):

Runxiang Qiu ◽

Qiu Runxiang ◽

Anqi Geng ◽

Jiancheng Liu ◽

C Wilson Xu ◽

...

Keyword(s):

Cell Division ◽

Progenitor Cells ◽

Neuronal Differentiation ◽

Cell Fate ◽

Neural Progenitor Cells ◽

Cortical Development ◽

Neural Progenitor ◽

Mammalian Brain ◽

Additional Cell ◽

A Cell

Abstract Balanced proliferation and differentiation of neural progenitor cells (NPCs) are critical for brain development, but how the process is regulated and what components of the cell division machinery is involved are not well understood. Here we report that SEPT7, a cell division regulator originally identified in Saccharomyces cerevisiae, interacts with KIF20A in the intercellular bridge of dividing NPCs and plays an essential role in maintaining the proliferative state of NPCs during cortical development. Knockdown of SEPT7 in NPCs results in displacement of KIF20A from the midbody and early neuronal differentiation. NPC-specific inducible knockout of Sept7 causes early cell cycle exit, precocious neuronal differentiation, and ventriculomegaly in the cortex, but surprisingly does not lead to noticeable cytokinesis defect. Our data uncover an interaction of SEPT7 and KIF20A during NPC divisions and demonstrate a crucial role of SEPT7 in cell fate determination. In addition, this study presents a functional approach for identifying additional cell fate regulators of the mammalian brain.

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Forcing neural progenitor cells to cycle is insufficient to alter cell-fate decision and timing of neuronal differentiation in the spinal cord

Neural Development ◽

10.1186/1749-8104-3-4 ◽

2008 ◽

Vol 3 (1) ◽

pp. 4 ◽

Cited By ~ 29

Author(s):

Valérie Lobjois ◽

Sophie Bel-Vialar ◽

Françoise Trousse ◽

Fabienne Pituello

Keyword(s):

Spinal Cord ◽

Progenitor Cells ◽

Neuronal Differentiation ◽

Cell Fate ◽

Neural Progenitor Cells ◽

Neural Progenitor ◽

Cell Fate Decision ◽

Fate Decision

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Hepatocyte Growth Factor Activator Inhibitor-1 Is Induced by Bone Morphogenetic Proteins and Regulates Proliferation and Cell Fate of Neural Progenitor Cells

PLoS ONE ◽

10.1371/journal.pone.0056117 ◽

2013 ◽

Vol 8 (2) ◽

pp. e56117 ◽

Cited By ~ 10

Author(s):

Raili Koivuniemi ◽

Johanna Mäkelä ◽

Marie-Estelle Hokkanen ◽

Céline Bruelle ◽

Tho Huu Ho ◽

...

Keyword(s):

Growth Factor ◽

Hepatocyte Growth Factor ◽

Progenitor Cells ◽

Cell Fate ◽

Bone Morphogenetic Proteins ◽

Neural Progenitor Cells ◽

Neural Progenitor ◽

Hepatocyte Growth Factor Activator ◽

Hepatocyte Growth ◽

Activator Inhibitor

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Propofol Affects Neurodegeneration and Neurogenesis by Regulation of Autophagy via Effects on Intracellular Calcium Homeostasis

Anesthesiology ◽

10.1097/aln.0000000000001730 ◽

2017 ◽

Vol 127 (3) ◽

pp. 490-501 ◽

Cited By ~ 21

Author(s):

Hui Qiao ◽

Yun Li ◽

Zhendong Xu ◽

Wenxian Li ◽

Zhijian Fu ◽

...

Keyword(s):

Cell Survival ◽

Progenitor Cells ◽

Cell Fate ◽

Calcium Concentration ◽

Neural Progenitor Cells ◽

Cytosolic Calcium ◽

Neural Progenitor ◽

Mediated Effects ◽

Proliferation And Differentiation ◽

Inositol 1,4,5 Trisphosphate

Abstract Background In human cortical neural progenitor cells, we investigated the effects of propofol on calcium homeostasis in both the ryanodine and inositol 1,4,5-trisphosphate calcium release channels. We also studied propofol-mediated effects on autophagy, cell survival, and neuro- and gliogenesis. Methods The dose–response relationship between propofol concentration and duration was studied in neural progenitor cells. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase release assays. The effects of propofol on cytosolic calcium concentration were evaluated using Fura-2, and autophagy activity was determined by LC3II expression levels with Western blot. Proliferation and differentiation were evaluated by bromodeoxyuridine incorporation and immunostaining with neuronal and glial markers. Results Propofol dose- and time-dependently induced cell damage and elevated LC3II expression, most robustly at 200 µM for 24 h (67 ± 11% of control, n = 12 to 19) and 6 h (2.4 ± 0.5 compared with 0.6 ± 0.1 of control, n = 7), respectively. Treatment with 200 μM propofol also increased cytosolic calcium concentration (346 ± 71% of control, n = 22 to 34). Propofol at 10 µM stimulated neural progenitor cell proliferation and promoted neuronal cell fate, whereas propofol at 200 µM impaired neuronal proliferation and promoted glial cell fate (n = 12 to 20). Cotreatment with ryanodine and inositol 1,4,5-trisphosphate receptor antagonists and inhibitors, cytosolic Ca2+ chelators, or autophagy inhibitors mostly mitigated the propofol-mediated effects on survival, proliferation, and differentiation. Conclusions These results suggest that propofol-mediated cell survival or neurogenesis is closely associated with propofol’s effects on autophagy by activation of ryanodine and inositol 1,4,5-trisphosphate receptors.

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Oxytocin alters cell fate selection of rat neural progenitor cells in vitro

PLoS ONE ◽

10.1371/journal.pone.0191160 ◽

2018 ◽

Vol 13 (1) ◽

pp. e0191160 ◽

Cited By ~ 7

Author(s):

Arvind Palanisamy ◽

Ramaswamy Kannappan ◽

Zhiqiang Xu ◽

Audrey Martino ◽

Matthew B. Friese ◽

...

Keyword(s):

Progenitor Cells ◽

Cell Fate ◽

Neural Progenitor Cells ◽

Neural Progenitor ◽

Selection Of

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Direct reprogramming of oligodendrocyte precursor cells into GABAergic inhibitory neurons by a single homeodomain transcription factor Dlx2

Scientific Reports ◽

10.1038/s41598-021-82931-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Linda L. Boshans ◽

Heun Soh ◽

William M. Wood ◽

Timothy M. Nolan ◽

Ion I. Mandoiu ◽

...

Keyword(s):

Transcription Factor ◽

Progenitor Cells ◽

Inhibitory Neuron ◽

Precursor Cells ◽

Synaptic Proteins ◽

Inhibitory Neurons ◽

Oligodendrocyte Precursor Cells ◽

Molecular Logic ◽

Neuronal Fate ◽

Oligodendrocyte Precursor

AbstractOligodendrocyte precursor cells (NG2 glia) are uniformly distributed proliferative cells in the mammalian central nervous system and generate myelinating oligodendrocytes throughout life. A subpopulation of OPCs in the neocortex arises from progenitor cells in the embryonic ganglionic eminences that also produce inhibitory neurons. The neuronal fate of some progenitor cells is sealed before birth as they become committed to the oligodendrocyte lineage, marked by sustained expression of the oligodendrocyte transcription factor Olig2, which represses the interneuron transcription factor Dlx2. Here we show that misexpression of Dlx2 alone in postnatal mouse OPCs caused them to switch their fate to GABAergic neurons within 2 days by downregulating Olig2 and upregulating a network of inhibitory neuron transcripts. After two weeks, some OPC-derived neurons generated trains of action potentials and formed clusters of GABAergic synaptic proteins. Our study revealed that the developmental molecular logic can be applied to promote neuronal reprogramming from OPCs.

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Hydrogel formulation determines cell fate of fetal and adult neural progenitor cells

Stem Cell Research ◽

10.1016/j.scr.2013.09.013 ◽

2014 ◽

Vol 12 (1) ◽

pp. 11-23 ◽

Cited By ~ 22

Author(s):

Emily R. Aurand ◽

Jennifer L. Wagner ◽

Robin Shandas ◽

Kimberly B. Bjugstad

Keyword(s):

Progenitor Cells ◽

Cell Fate ◽

Neural Progenitor Cells ◽

Neural Progenitor ◽

Hydrogel Formulation

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Differential Proliferation Rhythm of Neural Progenitor and Oligodendrocyte Precursor Cells in the Young Adult Hippocampus

PLoS ONE ◽

10.1371/journal.pone.0027628 ◽

2011 ◽

Vol 6 (11) ◽

pp. e27628 ◽

Cited By ~ 34

Author(s):

Yoko Matsumoto ◽

Yuji Tsunekawa ◽

Tadashi Nomura ◽

Fumikazu Suto ◽

Miho Matsumata ◽

...

Keyword(s):

Young Adult ◽

Neural Progenitor ◽

Precursor Cells ◽

Oligodendrocyte Precursor Cells ◽

Adult Hippocampus ◽

Oligodendrocyte Precursor

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BRCA1 and ELK-1 regulate Neural Progenitor Cell Fate in the Optic Tectum in response to Visual Experience in Xenopus laevis tadpoles

10.1101/2021.10.21.465368 ◽

2021 ◽

Author(s):

Lin-Chien Huang ◽

Haiyan He ◽

Aaron C. Ta ◽

Caroline R. McKeown ◽

Hollis T. Cline

Keyword(s):

Transcription Factor ◽

Progenitor Cells ◽

Cell Fate ◽

Optic Tectum ◽

Progenitor Cell ◽

Visual Experience ◽

Neural Progenitor Cells ◽

Neural Progenitor Cell ◽

Neural Progenitor

In developing Xenopus tadpoles, the optic tectum begins to receive patterned visual input while visuomotor circuits are still undergoing neurogenesis and circuit assembly. This visual input regulates neural progenitor cell fate decisions such that maintaining tadpoles in the dark increases proliferation, expanding the progenitor pool, while visual stimulation promotes neuronal differentiation. To identify regulators of activity-dependent neural progenitor cell fate, we used RNA-Seq to profile the transcriptomes of proliferating neural progenitor cells and newly-differentiated immature neurons. Out of 1,130 differentially expressed (DE) transcripts, we identified six DE transcription factors which are predicted to regulate the majority of the other DE transcripts. Here we focused on Breast cancer 1 (BRCA1) and the ETS-family transcription factor, ELK-1. BRCA1 is known for its role in cancers, but relatively little is known about its potential role in regulating neural progenitor cell fate. ELK-1 is a multifunctional transcription factor which regulates immediate early gene expression. We investigated the effect of BRCA1 and ELK-1 on activity-regulated neurogenesis in the tadpole visual system using in vivo timelapse imaging to monitor the fate of turbo-GFP-expressing SOX2+ neural progenitor cells in the optic tectum. Our longitudinal in vivo imaging analysis shows that knockdown of either BRCA1 or ELK-1 altered the fates of neural progenitor cells, and furthermore that the effects of visual experience on neurogenesis depend on BRCA1 expression, while the effects of visual experience on neuronal differentiation depend on ELK-1 expression. These studies provide insight into the potential mechanisms by which neural activity affects neural progenitor cell fate.

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