Histone Demethylase LSD1 Regulates Neural Stem Cell Proliferation

ABSTRACT Lysine-specific demethylase 1 (LSD1) functions as a transcriptional coregulator by modulating histone methylation. Its role in neural stem cells has not been studied. We show here for the first time that LSD1 serves as a key regulator of neural stem cell proliferation. Inhibition of LSD1 activity or knockdown of LSD1 expression led to dramatically reduced neural stem cell proliferation. LSD1 is recruited by nuclear receptor TLX, an essential neural stem cell regulator, to the promoters of TLX target genes to repress the expression of these genes, which are known regulators of cell proliferation. The importance of LSD1 function in neural stem cells was further supported by the observation that intracranial viral transduction of the LSD1 small interfering RNA (siRNA) or intraperitoneal injection of the LSD1 inhibitors pargyline and tranylcypromine led to dramatically reduced neural progenitor proliferation in the hippocampal dentate gyri of wild-type adult mouse brains. However, knockout of TLX expression abolished the inhibitory effect of pargyline and tranylcypromine on neural progenitor proliferation, suggesting that TLX is critical for the LSD1 inhibitor effect. These findings revealed a novel role for LSD1 in neural stem cell proliferation and uncovered a mechanism for neural stem cell proliferation through recruitment of LSD1 to modulate TLX activity.

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The Effect of Advanced Motherhood on Newborn Offspring’s Hippocampal Neural Stem Cell Proliferation

BioMed Research International ◽

10.1155/2016/6171352 ◽

2016 ◽

Vol 2016 ◽

pp. 1-7

Author(s):

Bo Li ◽

Ping Duan ◽

Xuefei Han ◽

Wenhai Yan ◽

Ying Xing

Keyword(s):

Cell Cycle ◽

Stem Cells ◽

Cell Proliferation ◽

Stem Cell ◽

Neural Stem Cell ◽

Control Group ◽

Stem Cell Proliferation ◽

Neural Stem Cell Proliferation ◽

Positive Rate ◽

Mother Group

Objective. To investigate the effect of advanced motherhood on rat hippocampal neural stem cell proliferation.Methods. Female parents were subdivided into control and old mother group by age, and neural stem cells were cultured from hippocampal tissues for 24 h newborn offspring. The diameter and numbers of neurospheres were examined by microscopy, and differences in proliferation were examined by EdU immunofluorescence, CCK-8 assay, and cell cycle analysis.Results. The number of neurospheres in the old mother group after culture was lower than the control group. Additionally, neurospheres’ diameter was smaller than that of the control group (P<0.05). The EdU positive rate of the old mother group was lower than that of the control group (P<0.05). CCK-8 assay results showed that the absorbance values for the old mother group were lower than that of the control group at 48 h and 72 h (P<0.05). The proportions of cells in the S and G2/M phases of the cell cycle for the older mother group were less than that found for the control group (P<0.05).Conclusion. The proliferation rates of hippocampal NSCs seen in the older mother group were lower than that seen in the control group.

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Imp/IGF2BP levels modulate individual neural stem cell growth and division through myc mRNA stability

10.1101/754382 ◽

2019 ◽

Cited By ~ 1

Author(s):

Tamsin J. Samuels ◽

Aino I. Järvelin ◽

David Ish-Horowicz ◽

Ilan Davis

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Neural Stem Cells ◽

Neural Stem Cell ◽

Mrna Stability ◽

Rna Binding ◽

Stem Cell Proliferation ◽

Neural Stem Cell Proliferation ◽

Protein Levels ◽

The Brain

ABSTRACTThe numerous neurons and glia that form the brain originate from tightly controlled growth and division of neural stem cells, regulated systemically by known extrinsic signals. However, the intrinsic mechanisms that control the characteristic proliferation rates of individual neural stem cells are unknown. Here, we show that the size and division rates of Drosophila neural stem cells (neuroblasts) are controlled by the highly conserved RNA binding protein Imp (IGF2BP), via one of its top binding targets in the brain, myc mRNA. We show that Imp stabilises myc mRNA leading to increased Myc protein levels, larger neuroblasts, and faster division rates. Declining Imp levels throughout development limit myc mRNA stability to restrain neuroblast growth and division, while heterogeneous Imp expression correlates with myc mRNA stability between individual neuroblasts in the brain. We propose that Imp-dependent regulation of myc mRNA stability fine-tunes individual neural stem cell proliferation rates.Abstract Figure

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Imp/IGF2BP levels modulate individual neural stem cell growth and division through myc mRNA stability

eLife ◽

10.7554/elife.51529 ◽

2020 ◽

Vol 9 ◽

Cited By ~ 9

Author(s):

Tamsin J Samuels ◽

Aino I Järvelin ◽

David Ish-Horowicz ◽

Ilan Davis

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Neural Stem Cells ◽

Neural Stem Cell ◽

Mrna Stability ◽

Rna Binding ◽

Stem Cell Proliferation ◽

Neural Stem Cell Proliferation ◽

Protein Levels ◽

The Brain

The numerous neurons and glia that form the brain originate from tightly controlled growth and division of neural stem cells, regulated systemically by important known stem cell-extrinsic signals. However, the cell-intrinsic mechanisms that control the distinctive proliferation rates of individual neural stem cells are unknown. Here, we show that the size and division rates of Drosophila neural stem cells (neuroblasts) are controlled by the highly conserved RNA binding protein Imp (IGF2BP), via one of its top binding targets in the brain, myc mRNA. We show that Imp stabilises myc mRNA leading to increased Myc protein levels, larger neuroblasts, and faster division rates. Declining Imp levels throughout development limit myc mRNA stability to restrain neuroblast growth and division, and heterogeneous Imp expression correlates with myc mRNA stability between individual neuroblasts in the brain. We propose that Imp-dependent regulation of myc mRNA stability fine-tunes individual neural stem cell proliferation rates.

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