Genetic fate mapping of Olig2 progenitors in the injured adult cerebral cortex reveals preferential differentiation into astrocytes
Olig2 is a basic helix‐loop‐helix (bHLH) transcription factor essential for development of motoneurons and oligodendrocytes. It is known that Olig2+ cells persist in the central nervous system (CNS) from embryonic to adult stages and that the number of Olig2+ progenitors increases in the injured adu...
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| Veröffentlicht in: | Journal of neuroscience research 2008-12, Vol.86 (16), p.3494-3502 |
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| creator | Tatsumi, Kouko Takebayashi, Hirohide Manabe, Takayuki Tanaka, Kenji F. Makinodan, Manabu Yamauchi, Takahira Makinodan, Eri Matsuyoshi, Hiroko Okuda, Hiroaki Ikenaka, Kazuhiro Wanaka, Akio |
| description | Olig2 is a basic helix‐loop‐helix (bHLH) transcription factor essential for development of motoneurons and oligodendrocytes. It is known that Olig2+ cells persist in the central nervous system (CNS) from embryonic to adult stages and that the number of Olig2+ progenitors increases in the injured adult CNS. Recent studies have demonstrated an inhibitory action of Olig2 on neurogenesis in adult CNS, but the fate of Olig2+ cells in the injured state remains largely unknown. To trace directly the fate of Olig2 cells in the adult cerebral cortex after injury, we employed the CreER/loxP system to target the olig2 locus. In this genetic tracing study, green fluorescent protein (GFP) reporter‐positive cells labeled after cryoinjury coexpressed glial fibrillary acidic protein (GFAP), an astrocytic marker. Electron microscopy also showed that GFP+ cells have the ultrastructural characteristics of astrocytes. Furthermore, GFP+ cells labeled before injury, most of which had been NG2 cells, also produced bushy astrocytes. Here we show direct evidence that Olig2+ cells preferentially differentiate into astrocytes, which strongly express GFAP, in response to injury in the adult cerebral cortex. These results suggest that reactive astrocytes, known to be the main contributors to glial scars, originate, at least in part, from Olig2+ cells. © 2008 Wiley‐Liss, Inc. |
| doi_str_mv | 10.1002/jnr.21862 |
| format | Article |
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It is known that Olig2+ cells persist in the central nervous system (CNS) from embryonic to adult stages and that the number of Olig2+ progenitors increases in the injured adult CNS. Recent studies have demonstrated an inhibitory action of Olig2 on neurogenesis in adult CNS, but the fate of Olig2+ cells in the injured state remains largely unknown. To trace directly the fate of Olig2 cells in the adult cerebral cortex after injury, we employed the CreER/loxP system to target the olig2 locus. In this genetic tracing study, green fluorescent protein (GFP) reporter‐positive cells labeled after cryoinjury coexpressed glial fibrillary acidic protein (GFAP), an astrocytic marker. Electron microscopy also showed that GFP+ cells have the ultrastructural characteristics of astrocytes. Furthermore, GFP+ cells labeled before injury, most of which had been NG2 cells, also produced bushy astrocytes. Here we show direct evidence that Olig2+ cells preferentially differentiate into astrocytes, which strongly express GFAP, in response to injury in the adult cerebral cortex. These results suggest that reactive astrocytes, known to be the main contributors to glial scars, originate, at least in part, from Olig2+ cells. © 2008 Wiley‐Liss, Inc.</description><identifier>ISSN: 0360-4012</identifier><identifier>EISSN: 1097-4547</identifier><identifier>DOI: 10.1002/jnr.21862</identifier><identifier>PMID: 18816798</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>adult cerebral cortex ; Animals ; Antigens - metabolism ; astrocyte ; Astrocytes - metabolism ; Astrocytes - ultrastructure ; Basic Helix-Loop-Helix Transcription Factors - genetics ; Biomarkers - analysis ; Biomarkers - metabolism ; Brain Injuries - genetics ; Brain Injuries - metabolism ; Brain Injuries - physiopathology ; Cell Differentiation - genetics ; Cell Lineage - genetics ; Chromosome Mapping - methods ; Cicatrix - genetics ; Cicatrix - metabolism ; Cicatrix - physiopathology ; CreER/loxP system ; Cryosurgery - methods ; Gene Knock-In Techniques ; Genes, Reporter - genetics ; Glial Fibrillary Acidic Protein - genetics ; Glial Fibrillary Acidic Protein - metabolism ; Gliosis - genetics ; Gliosis - metabolism ; Gliosis - physiopathology ; Green Fluorescent Proteins - genetics ; Mice ; Mice, Transgenic ; Microscopy, Electron, Transmission ; Nerve Tissue Proteins - genetics ; Olig2 ; Oligodendrocyte Transcription Factor 2 ; progenitor cells ; Proteoglycans - metabolism ; Stem Cells - metabolism ; Stem Cells - ultrastructure</subject><ispartof>Journal of neuroscience research, 2008-12, Vol.86 (16), p.3494-3502</ispartof><rights>Copyright © 2008 Wiley‐Liss, Inc.</rights><rights>(c) 2008 Wiley-Liss, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3612-f55026b17b3d6bc6cf2f1d80a5e8e0ba34945c20f084842a8c2802498fb5db8e3</citedby><cites>FETCH-LOGICAL-c3612-f55026b17b3d6bc6cf2f1d80a5e8e0ba34945c20f084842a8c2802498fb5db8e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjnr.21862$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjnr.21862$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1416,27923,27924,45573,45574</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18816798$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tatsumi, Kouko</creatorcontrib><creatorcontrib>Takebayashi, Hirohide</creatorcontrib><creatorcontrib>Manabe, Takayuki</creatorcontrib><creatorcontrib>Tanaka, Kenji F.</creatorcontrib><creatorcontrib>Makinodan, Manabu</creatorcontrib><creatorcontrib>Yamauchi, Takahira</creatorcontrib><creatorcontrib>Makinodan, Eri</creatorcontrib><creatorcontrib>Matsuyoshi, Hiroko</creatorcontrib><creatorcontrib>Okuda, Hiroaki</creatorcontrib><creatorcontrib>Ikenaka, Kazuhiro</creatorcontrib><creatorcontrib>Wanaka, Akio</creatorcontrib><title>Genetic fate mapping of Olig2 progenitors in the injured adult cerebral cortex reveals preferential differentiation into astrocytes</title><title>Journal of neuroscience research</title><addtitle>J. Neurosci. Res</addtitle><description>Olig2 is a basic helix‐loop‐helix (bHLH) transcription factor essential for development of motoneurons and oligodendrocytes. It is known that Olig2+ cells persist in the central nervous system (CNS) from embryonic to adult stages and that the number of Olig2+ progenitors increases in the injured adult CNS. Recent studies have demonstrated an inhibitory action of Olig2 on neurogenesis in adult CNS, but the fate of Olig2+ cells in the injured state remains largely unknown. To trace directly the fate of Olig2 cells in the adult cerebral cortex after injury, we employed the CreER/loxP system to target the olig2 locus. In this genetic tracing study, green fluorescent protein (GFP) reporter‐positive cells labeled after cryoinjury coexpressed glial fibrillary acidic protein (GFAP), an astrocytic marker. Electron microscopy also showed that GFP+ cells have the ultrastructural characteristics of astrocytes. Furthermore, GFP+ cells labeled before injury, most of which had been NG2 cells, also produced bushy astrocytes. Here we show direct evidence that Olig2+ cells preferentially differentiate into astrocytes, which strongly express GFAP, in response to injury in the adult cerebral cortex. These results suggest that reactive astrocytes, known to be the main contributors to glial scars, originate, at least in part, from Olig2+ cells. © 2008 Wiley‐Liss, Inc.</description><subject>adult cerebral cortex</subject><subject>Animals</subject><subject>Antigens - metabolism</subject><subject>astrocyte</subject><subject>Astrocytes - metabolism</subject><subject>Astrocytes - ultrastructure</subject><subject>Basic Helix-Loop-Helix Transcription Factors - genetics</subject><subject>Biomarkers - analysis</subject><subject>Biomarkers - metabolism</subject><subject>Brain Injuries - genetics</subject><subject>Brain Injuries - metabolism</subject><subject>Brain Injuries - physiopathology</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Lineage - genetics</subject><subject>Chromosome Mapping - methods</subject><subject>Cicatrix - genetics</subject><subject>Cicatrix - metabolism</subject><subject>Cicatrix - physiopathology</subject><subject>CreER/loxP system</subject><subject>Cryosurgery - methods</subject><subject>Gene Knock-In Techniques</subject><subject>Genes, Reporter - genetics</subject><subject>Glial Fibrillary Acidic Protein - genetics</subject><subject>Glial Fibrillary Acidic Protein - metabolism</subject><subject>Gliosis - genetics</subject><subject>Gliosis - metabolism</subject><subject>Gliosis - physiopathology</subject><subject>Green Fluorescent Proteins - genetics</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Microscopy, Electron, Transmission</subject><subject>Nerve Tissue Proteins - genetics</subject><subject>Olig2</subject><subject>Oligodendrocyte Transcription Factor 2</subject><subject>progenitor cells</subject><subject>Proteoglycans - metabolism</subject><subject>Stem Cells - metabolism</subject><subject>Stem Cells - ultrastructure</subject><issn>0360-4012</issn><issn>1097-4547</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kE2P0zAQhi0EYsvCgT-AfELikN2xnTjOEVVQPla7ogJxtBxnXFzSuGs7QM_8cQztwonTaDTP-0rzEPKUwQUD4JfbKV5wpiS_RxYMuraqm7q9TxYgJFQ1MH5GHqW0BYCua8RDcsaUYrLt1IL8XOGE2VvqTEa6M_u9nzY0OHoz-g2n-xg2OPkcYqJ-ovkLlrGdIw7UDPOYqcWIfTQjtSFm_EEjfkMzphJEV05T9uU2eHe3ZB-mUpEDNSnHYA8Z02PywJUMPjnNc_Lp9auPyzfV1c3q7fLlVWWFZLxyTQNc9qztxSB7K63jjg0KTIMKoTei7urGcnCgalVzoyxXwOtOub4ZeoXinDw_9pavbmdMWe98sjiOZsIwJy07xQTUbQFfHEEbQ0rlE72PfmfiQTPQv43rYlz_MV7YZ6fSud_h8I88KS7A5RH47kc8_L9Jv7te31VWx4RPRenfhIlftWxF2-jP1yvN1sv2w3LN9XvxC1vLnLc</recordid><startdate>200812</startdate><enddate>200812</enddate><creator>Tatsumi, Kouko</creator><creator>Takebayashi, Hirohide</creator><creator>Manabe, Takayuki</creator><creator>Tanaka, Kenji F.</creator><creator>Makinodan, Manabu</creator><creator>Yamauchi, Takahira</creator><creator>Makinodan, Eri</creator><creator>Matsuyoshi, Hiroko</creator><creator>Okuda, Hiroaki</creator><creator>Ikenaka, Kazuhiro</creator><creator>Wanaka, Akio</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>200812</creationdate><title>Genetic fate mapping of Olig2 progenitors in the injured adult cerebral cortex reveals preferential differentiation into astrocytes</title><author>Tatsumi, Kouko ; Takebayashi, Hirohide ; Manabe, Takayuki ; Tanaka, Kenji F. ; Makinodan, Manabu ; Yamauchi, Takahira ; Makinodan, Eri ; Matsuyoshi, Hiroko ; Okuda, Hiroaki ; Ikenaka, Kazuhiro ; Wanaka, Akio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3612-f55026b17b3d6bc6cf2f1d80a5e8e0ba34945c20f084842a8c2802498fb5db8e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>adult cerebral cortex</topic><topic>Animals</topic><topic>Antigens - metabolism</topic><topic>astrocyte</topic><topic>Astrocytes - metabolism</topic><topic>Astrocytes - ultrastructure</topic><topic>Basic Helix-Loop-Helix Transcription Factors - genetics</topic><topic>Biomarkers - analysis</topic><topic>Biomarkers - metabolism</topic><topic>Brain Injuries - genetics</topic><topic>Brain Injuries - metabolism</topic><topic>Brain Injuries - physiopathology</topic><topic>Cell Differentiation - genetics</topic><topic>Cell Lineage - genetics</topic><topic>Chromosome Mapping - methods</topic><topic>Cicatrix - genetics</topic><topic>Cicatrix - metabolism</topic><topic>Cicatrix - physiopathology</topic><topic>CreER/loxP system</topic><topic>Cryosurgery - methods</topic><topic>Gene Knock-In Techniques</topic><topic>Genes, Reporter - genetics</topic><topic>Glial Fibrillary Acidic Protein - genetics</topic><topic>Glial Fibrillary Acidic Protein - metabolism</topic><topic>Gliosis - genetics</topic><topic>Gliosis - metabolism</topic><topic>Gliosis - physiopathology</topic><topic>Green Fluorescent Proteins - genetics</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Microscopy, Electron, Transmission</topic><topic>Nerve Tissue Proteins - genetics</topic><topic>Olig2</topic><topic>Oligodendrocyte Transcription Factor 2</topic><topic>progenitor cells</topic><topic>Proteoglycans - metabolism</topic><topic>Stem Cells - metabolism</topic><topic>Stem Cells - ultrastructure</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tatsumi, Kouko</creatorcontrib><creatorcontrib>Takebayashi, Hirohide</creatorcontrib><creatorcontrib>Manabe, Takayuki</creatorcontrib><creatorcontrib>Tanaka, Kenji F.</creatorcontrib><creatorcontrib>Makinodan, Manabu</creatorcontrib><creatorcontrib>Yamauchi, Takahira</creatorcontrib><creatorcontrib>Makinodan, Eri</creatorcontrib><creatorcontrib>Matsuyoshi, Hiroko</creatorcontrib><creatorcontrib>Okuda, Hiroaki</creatorcontrib><creatorcontrib>Ikenaka, Kazuhiro</creatorcontrib><creatorcontrib>Wanaka, Akio</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of neuroscience research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tatsumi, Kouko</au><au>Takebayashi, Hirohide</au><au>Manabe, Takayuki</au><au>Tanaka, Kenji F.</au><au>Makinodan, Manabu</au><au>Yamauchi, Takahira</au><au>Makinodan, Eri</au><au>Matsuyoshi, Hiroko</au><au>Okuda, Hiroaki</au><au>Ikenaka, Kazuhiro</au><au>Wanaka, Akio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic fate mapping of Olig2 progenitors in the injured adult cerebral cortex reveals preferential differentiation into astrocytes</atitle><jtitle>Journal of neuroscience research</jtitle><addtitle>J. Neurosci. Res</addtitle><date>2008-12</date><risdate>2008</risdate><volume>86</volume><issue>16</issue><spage>3494</spage><epage>3502</epage><pages>3494-3502</pages><issn>0360-4012</issn><eissn>1097-4547</eissn><abstract>Olig2 is a basic helix‐loop‐helix (bHLH) transcription factor essential for development of motoneurons and oligodendrocytes. It is known that Olig2+ cells persist in the central nervous system (CNS) from embryonic to adult stages and that the number of Olig2+ progenitors increases in the injured adult CNS. Recent studies have demonstrated an inhibitory action of Olig2 on neurogenesis in adult CNS, but the fate of Olig2+ cells in the injured state remains largely unknown. To trace directly the fate of Olig2 cells in the adult cerebral cortex after injury, we employed the CreER/loxP system to target the olig2 locus. In this genetic tracing study, green fluorescent protein (GFP) reporter‐positive cells labeled after cryoinjury coexpressed glial fibrillary acidic protein (GFAP), an astrocytic marker. Electron microscopy also showed that GFP+ cells have the ultrastructural characteristics of astrocytes. Furthermore, GFP+ cells labeled before injury, most of which had been NG2 cells, also produced bushy astrocytes. Here we show direct evidence that Olig2+ cells preferentially differentiate into astrocytes, which strongly express GFAP, in response to injury in the adult cerebral cortex. These results suggest that reactive astrocytes, known to be the main contributors to glial scars, originate, at least in part, from Olig2+ cells. © 2008 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>18816798</pmid><doi>10.1002/jnr.21862</doi><tpages>9</tpages></addata></record> |
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| subjects | adult cerebral cortex Animals Antigens - metabolism astrocyte Astrocytes - metabolism Astrocytes - ultrastructure Basic Helix-Loop-Helix Transcription Factors - genetics Biomarkers - analysis Biomarkers - metabolism Brain Injuries - genetics Brain Injuries - metabolism Brain Injuries - physiopathology Cell Differentiation - genetics Cell Lineage - genetics Chromosome Mapping - methods Cicatrix - genetics Cicatrix - metabolism Cicatrix - physiopathology CreER/loxP system Cryosurgery - methods Gene Knock-In Techniques Genes, Reporter - genetics Glial Fibrillary Acidic Protein - genetics Glial Fibrillary Acidic Protein - metabolism Gliosis - genetics Gliosis - metabolism Gliosis - physiopathology Green Fluorescent Proteins - genetics Mice Mice, Transgenic Microscopy, Electron, Transmission Nerve Tissue Proteins - genetics Olig2 Oligodendrocyte Transcription Factor 2 progenitor cells Proteoglycans - metabolism Stem Cells - metabolism Stem Cells - ultrastructure |
| title | Genetic fate mapping of Olig2 progenitors in the injured adult cerebral cortex reveals preferential differentiation into astrocytes |
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