Lsh/HELLS regulates self-renewal/proliferation of neural stem/progenitor cells associated with control of Bmp4 and Cdkn1a expression

Authors

• Y Han
• J Ren
• E Lee
• W Yu
• K Muegge

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 dysmorphism (ICF) syndrome associated with neurologic deficiencies. We report here a critical role for Lsh in murine neural development. Ablation of Lsh alters epigenetic states at specific enhancer regions of key cell cycle regulators and stem cell regulators in neural stem/progenitor cells (NSPCs) and leads to their abnormal expression. As a consequence, Lsh depleted NSPCs display reduced growth, increases in apoptosis and impaired ability of self-renewal. Addition of the stem cell regulator Bmp4 can restore growth repression in Lsh depleted NSPCs. These results corroborate that Lsh exerts epigenetic regulation at key regulators of neural stem cell fate ensuring adequate NSPC self-renewal and maintenance during development.

Scientific Focus Area: Stem Cell Biology

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