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Status |
Public on May 02, 2014 |
Title |
Dual and separable roles for Ezh2 in neurogenic astroglia |
Organism |
Mus musculus |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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Summary |
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 that specify 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.
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Overall design |
Examination of histone modifications (H3K27me3 and H3K4me3) in subventricular zone neural stem cells
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Contributor(s) |
Lim DA, Hwang WW, Salinas RD, Delgado RN |
Citation(s) |
24867641 |
Submission date |
Apr 01, 2014 |
Last update date |
May 15, 2019 |
Contact name |
Daniel A Lim |
E-mail(s) |
LimD@neurosurg.ucsf.edu
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Phone |
415-353-3935
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Organization name |
University of California, San Francisco
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Department |
Neurological Surgery
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Lab |
Lim Lab
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Street address |
35 Medical Center Way RMB 933B
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City |
San Francisco |
State/province |
CA |
ZIP/Postal code |
94143 |
Country |
USA |
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Platforms (1) |
GPL9185 |
Illumina Genome Analyzer (Mus musculus) |
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Samples (6)
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Relations |
BioProject |
PRJNA243128 |
SRA |
SRP040763 |