Distinct and separable roles for EZH2 in neurogenic astroglia.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 24867641.
- Also identified by DOI 10.7554/eLife.02439 and PMC identifier 4032491.
- Licence recorded as CC0.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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.DOI: http://dx.doi.org/10.7554/eLife.02439.001.
Medical subject headings
- Astrocytes
- Neurogenesis
- Polycomb Repressive Complex 2