Distinct and separable roles for EZH2 in neurogenic astroglia

eLife

Michael C Oldham¹  Jason J Siu¹  Ryan N Delgado¹  Ryan D Salinas²  Arturo Alvarez-Buylla²  William W Hwang³  Kevin W Kelley³  Mercedes F Paredes³  Daniel A Lim⁴ 

[1] Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, USA;Veterans Affairs Medical Center, University of California, San Francisco, San Francisco, USA;Department of Neurological Surgery, University of California, San Francisco, San Francisco, United States;Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, USA;

关键词: EZH2;    Polycomb;    SVZ neurogenesis;    glioma;    astrocyte heterogeneity;    OLIG2;   

DOI  :  10.7554/eLife.02439

来源: DOAJ

【 摘 要 】

The epigenetic mechanisms that enable specialized astrocytes to retain neurogenic competence throughout adult life are still poorly understood. Here we show that astrocytes that serve as neural stem cells (NSCs) in the adult mouse subventricular zone (SVZ) express the histone methyltransferase EZH2. This Polycomb repressive factor is required for neurogenesis independent of its role in SVZ NSC proliferation, as Ink4a/Arf-deficiency in Ezh2-deleted SVZ NSCs rescues cell proliferation, but neurogenesis remains defective. Olig2 is a direct target of EZH2, and repression of this bHLH transcription factor is critical for neuronal differentiation. Furthermore, Ezh2 prevents the inappropriate activation of genes associated with non-SVZ neuronal subtypes. In the human brain, SVZ cells including local astroglia also express EZH2, correlating with postnatal neurogenesis. Thus, EZH2 is an epigenetic regulator that distinguishes neurogenic SVZ astrocytes, orchestrating distinct and separable aspects of adult stem cell biology, which has important implications for regenerative medicine and oncogenesis.

【 授权许可】

Unknown