Distinct and separable roles for EZH2 in neurogenic astroglia
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....
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2014-05-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/02439 |
| _version_ | 1818018596453875712 |
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| author | William W Hwang Ryan D Salinas Jason J Siu Kevin W Kelley Ryan N Delgado Mercedes F Paredes Arturo Alvarez-Buylla Michael C Oldham Daniel A Lim |
| author_facet | William W Hwang Ryan D Salinas Jason J Siu Kevin W Kelley Ryan N Delgado Mercedes F Paredes Arturo Alvarez-Buylla Michael C Oldham Daniel A Lim |
| author_sort | William W Hwang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T07:41:44Z |
| format | Article |
| id | doaj.art-cb1ed4213f4c459aa9c851f670048417 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:41:44Z |
| publishDate | 2014-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-cb1ed4213f4c459aa9c851f6700484172022-12-22T02:05:29ZengeLife Sciences Publications LtdeLife2050-084X2014-05-01310.7554/eLife.02439Distinct and separable roles for EZH2 in neurogenic astrogliaWilliam W Hwang0Ryan D Salinas1Jason J Siu2Kevin W Kelley3Ryan N Delgado4Mercedes F Paredes5Arturo Alvarez-Buylla6Michael C Oldham7Daniel A Lim8Department of Neurological Surgery, University of California, San Francisco, San Francisco, United States; Veterans Affairs Medical Center, University of California, San Francisco, San Francisco, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, USADepartment 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, USADepartment of Neurological Surgery, University of California, San Francisco, San Francisco, United States; Veterans Affairs Medical Center, University of California, San Francisco, San Francisco, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, USAEli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, USA; Department of Pediatrics, University of California, San Francisco, San Francisco, United StatesDepartment 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, USADepartment 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; Department of Neurology, University of California, San Francisco, San Francisco, United StatesDepartment 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, USAEli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, USA; Department of Neurology, University of California, San Francisco, San Francisco, United StatesDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, United States; Veterans Affairs Medical Center, University of California, San Francisco, San Francisco, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, USAThe 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.https://elifesciences.org/articles/02439EZH2PolycombSVZ neurogenesisgliomaastrocyte heterogeneityOLIG2 |
| spellingShingle | William W Hwang Ryan D Salinas Jason J Siu Kevin W Kelley Ryan N Delgado Mercedes F Paredes Arturo Alvarez-Buylla Michael C Oldham Daniel A Lim Distinct and separable roles for EZH2 in neurogenic astroglia eLife EZH2 Polycomb SVZ neurogenesis glioma astrocyte heterogeneity OLIG2 |
| title | Distinct and separable roles for EZH2 in neurogenic astroglia |
| title_full | Distinct and separable roles for EZH2 in neurogenic astroglia |
| title_fullStr | Distinct and separable roles for EZH2 in neurogenic astroglia |
| title_full_unstemmed | Distinct and separable roles for EZH2 in neurogenic astroglia |
| title_short | Distinct and separable roles for EZH2 in neurogenic astroglia |
| title_sort | distinct and separable roles for ezh2 in neurogenic astroglia |
| topic | EZH2 Polycomb SVZ neurogenesis glioma astrocyte heterogeneity OLIG2 |
| url | https://elifesciences.org/articles/02439 |
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