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Lsh/HELLS regulates self-renewal/proliferation of neural stem/progenitor cells

  1. Author:
    Han, Yixing
    Ren, Jianke
    Lee, Eunice
    Xu, Xiaoping
    Yu, Weishi
    Muegge, Kathrin

  2. Author Address

    NCI, Mouse Canc Genet Program, Ctr Canc Res, Ft Detrick, MD 21702 USA.Leidos Biomed Res Inc, Basic Sci Program, Mouse Canc Genet Program, Frederick Natl Lab Canc Res, Ft Detrick, MD 21702 USA.
    1. Year: 2017
    2. Date: Apr 25
  2. Journal: SCIENTIFIC REPORTS
  3. NATURE PUBLISHING GROUP,
    1. 7
    2. 1
    3. Pages: 1136
  5. Type of Article: Article
  6. Article Number: ARTN 1136
  7. ISSN: 2045-2322
  1. Abstract:

    Epigenetic mechanisms are known to exert control over gene expression and determine cell fate. Genetic mutations in epigenetic regulators are responsible for several neurologic disorders. Mutations of the chromatin remodeling protein Lsh/HELLS can cause the human Immunodeficiency, Centromere instability and Facial anomalies (ICF) syndrome, which is associated with neurologic deficiencies. We report here a critical role for Lsh in murine neural development. Lsh depleted neural stem/progenitor cells (NSPCs) display reduced growth, increases in apoptosis and impaired ability of self-renewal. RNA-seq analysis demonstrates differential gene expression in Lsh-/-NSPCs and suggests multiple aberrant pathways. Concentrating on specific genomic targets, we show that ablation of Lsh alters epigenetic states at specific enhancer regions of the key cell cycle regulator Cdkn1a and the stem cell regulator Bmp4 in NSPCs and alters their expression. These results suggest that Lsh exerts epigenetic regulation at key regulators of neural stem cell fate ensuring adequate NSPCs self-renewal and maintenance during development.

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External Sources

  1. View Full Text
  2. DOI: 10.1038/s41598-017-00804-6
  3. PMID: 28442710
  4. PMCID: PMC5430779
  5. View record in Web of Science®
  6. WOS: 000400104200025

Library Notes

  1. Fiscal Year: FY2016-2017
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