Paired related homeobox protein 1 is a regulator of stemness in adult neural stem/progenitor cells
Newborn neurons are generated from neural stem cells (NSCs) in two major niches of the adult brain. Maintenance of self-renewal and multipotency of adult NSCs is controlled by multiple transcription factor networks. We show here that paired related homeobox protein Prx1 (MHox1/Prrx1) plays an import...
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| Veröffentlicht in: | The Journal of neuroscience 2013-02, Vol.33 (9), p.4066-4075 |
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| container_title | The Journal of neuroscience |
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| creator | Shimozaki, Koji Clemenson, Jr, Gregory D Gage, Fred H |
| description | Newborn neurons are generated from neural stem cells (NSCs) in two major niches of the adult brain. Maintenance of self-renewal and multipotency of adult NSCs is controlled by multiple transcription factor networks. We show here that paired related homeobox protein Prx1 (MHox1/Prrx1) plays an important role in the maintenance of adult NSCs. Prx1 works with the transcription factor Sox2 as a coactivator, and depletion of Prx1 in cultured adult mouse NSCs reduces their self-renewal. In addition, we find that Prx1 protein is expressed in Sox2(+)/GFAP(+)/Nestin(+) astrocytes in the germinal regions of the adult mouse forebrain. The continuous expression of Prx1 in proliferating adult mouse hippocampal stem/progenitor cells in vivo leads to the generation of radial/horizontal-shaped astrocyte progenitor- and oligodendrocyte progenitor-like cells with no newborn neurons in the neurogenic niche. These data suggest that Prx1 plays an important role as a key switch for neural cell lineage determination and the maintenance of the self-renewal of adult NSCs at several stages in the adult brain. |
| doi_str_mv | 10.1523/JNEUROSCI.4586-12.2013 |
| format | Article |
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Maintenance of self-renewal and multipotency of adult NSCs is controlled by multiple transcription factor networks. We show here that paired related homeobox protein Prx1 (MHox1/Prrx1) plays an important role in the maintenance of adult NSCs. Prx1 works with the transcription factor Sox2 as a coactivator, and depletion of Prx1 in cultured adult mouse NSCs reduces their self-renewal. In addition, we find that Prx1 protein is expressed in Sox2(+)/GFAP(+)/Nestin(+) astrocytes in the germinal regions of the adult mouse forebrain. The continuous expression of Prx1 in proliferating adult mouse hippocampal stem/progenitor cells in vivo leads to the generation of radial/horizontal-shaped astrocyte progenitor- and oligodendrocyte progenitor-like cells with no newborn neurons in the neurogenic niche. These data suggest that Prx1 plays an important role as a key switch for neural cell lineage determination and the maintenance of the self-renewal of adult NSCs at several stages in the adult brain.</description><identifier>ISSN: 0270-6474</identifier><identifier>ISSN: 1529-2401</identifier><identifier>EISSN: 1529-2401</identifier><identifier>DOI: 10.1523/JNEUROSCI.4586-12.2013</identifier><identifier>PMID: 23447615</identifier><language>eng</language><publisher>United States: Society for Neuroscience</publisher><subject>Adult Stem Cells - physiology ; Animals ; Astrocytes - physiology ; Bromodeoxyuridine ; Caspase 3 - metabolism ; Cell Differentiation - genetics ; Cell Proliferation ; Cells, Cultured ; Female ; Gene Expression Profiling ; Gene Expression Regulation - genetics ; Gene Expression Regulation - physiology ; Green Fluorescent Proteins - genetics ; Green Fluorescent Proteins - metabolism ; Homeodomain Proteins - genetics ; Homeodomain Proteins - metabolism ; Humans ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Nerve Tissue Proteins - metabolism ; Neurons - physiology ; Oligonucleotide Array Sequence Analysis ; Prosencephalon - cytology ; Rats ; RNA, Messenger - metabolism ; RNA, Small Interfering - metabolism ; SOXB1 Transcription Factors - metabolism ; Transfection ; Two-Hybrid System Techniques</subject><ispartof>The Journal of neuroscience, 2013-02, Vol.33 (9), p.4066-4075</ispartof><rights>Copyright © 2013 the authors 0270-6474/13/334066-10$15.00/0 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c513t-a337f5502e79f8d6ea1ef5f966e947ee14e05e04c24d4010ceeec42df14d7ce53</citedby><cites>FETCH-LOGICAL-c513t-a337f5502e79f8d6ea1ef5f966e947ee14e05e04c24d4010ceeec42df14d7ce53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6619329/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6619329/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27922,27923,53789,53791</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23447615$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shimozaki, Koji</creatorcontrib><creatorcontrib>Clemenson, Jr, Gregory D</creatorcontrib><creatorcontrib>Gage, Fred H</creatorcontrib><title>Paired related homeobox protein 1 is a regulator of stemness in adult neural stem/progenitor cells</title><title>The Journal of neuroscience</title><addtitle>J Neurosci</addtitle><description>Newborn neurons are generated from neural stem cells (NSCs) in two major niches of the adult brain. Maintenance of self-renewal and multipotency of adult NSCs is controlled by multiple transcription factor networks. We show here that paired related homeobox protein Prx1 (MHox1/Prrx1) plays an important role in the maintenance of adult NSCs. Prx1 works with the transcription factor Sox2 as a coactivator, and depletion of Prx1 in cultured adult mouse NSCs reduces their self-renewal. In addition, we find that Prx1 protein is expressed in Sox2(+)/GFAP(+)/Nestin(+) astrocytes in the germinal regions of the adult mouse forebrain. The continuous expression of Prx1 in proliferating adult mouse hippocampal stem/progenitor cells in vivo leads to the generation of radial/horizontal-shaped astrocyte progenitor- and oligodendrocyte progenitor-like cells with no newborn neurons in the neurogenic niche. These data suggest that Prx1 plays an important role as a key switch for neural cell lineage determination and the maintenance of the self-renewal of adult NSCs at several stages in the adult brain.</description><subject>Adult Stem Cells - physiology</subject><subject>Animals</subject><subject>Astrocytes - physiology</subject><subject>Bromodeoxyuridine</subject><subject>Caspase 3 - metabolism</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Proliferation</subject><subject>Cells, Cultured</subject><subject>Female</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation - genetics</subject><subject>Gene Expression Regulation - physiology</subject><subject>Green Fluorescent Proteins - genetics</subject><subject>Green Fluorescent Proteins - metabolism</subject><subject>Homeodomain Proteins - genetics</subject><subject>Homeodomain Proteins - metabolism</subject><subject>Humans</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>Neurons - physiology</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Prosencephalon - cytology</subject><subject>Rats</subject><subject>RNA, Messenger - metabolism</subject><subject>RNA, Small Interfering - metabolism</subject><subject>SOXB1 Transcription Factors - metabolism</subject><subject>Transfection</subject><subject>Two-Hybrid System Techniques</subject><issn>0270-6474</issn><issn>1529-2401</issn><issn>1529-2401</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUUtP20AQXqEiEtL-BbTHXhx29hlfkKqIR1AEiJbzamOPg5HtTXftqvx71jwiOM3he8w38xFyAmwOiovT65vzh_vb38vVXKqFzoDPOQNxQKYJzTMuGXwjU8YNy7Q0ckKOY3xijBkG5ohMuJDSaFBTsrlzdcCSBmxcn-ajb9Fv_H-6C77HuqNA60hdwrdDYvhAfUVjj22HMdKEu3JoetrhEFzzCpwm5Ra7euQW2DTxOzmsXBPxx_uckYeL8z_Lq2x9e7la_lpnhQLRZ04IUynFOJq8WpQaHWClqlxrzKVBBIlMIZMFl2U6jxWIWEheViBLU6ASM3L25rsbNi2WBXZ9ymR3oW5deLbe1fYr0tWPduv_Wa0hFzxPBj_fDYL_O2DsbVvH8QTXoR-iBaVApzenuDOi36hF8DEGrPZrgNmxILsvyI4FWeB2LCgJTz6H3Ms-GhEvUvCQCw</recordid><startdate>20130227</startdate><enddate>20130227</enddate><creator>Shimozaki, Koji</creator><creator>Clemenson, Jr, Gregory D</creator><creator>Gage, Fred H</creator><general>Society for Neuroscience</general><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>7TK</scope><scope>5PM</scope></search><sort><creationdate>20130227</creationdate><title>Paired related homeobox protein 1 is a regulator of stemness in adult neural stem/progenitor cells</title><author>Shimozaki, Koji ; Clemenson, Jr, Gregory D ; Gage, Fred H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c513t-a337f5502e79f8d6ea1ef5f966e947ee14e05e04c24d4010ceeec42df14d7ce53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adult Stem Cells - physiology</topic><topic>Animals</topic><topic>Astrocytes - physiology</topic><topic>Bromodeoxyuridine</topic><topic>Caspase 3 - metabolism</topic><topic>Cell Differentiation - genetics</topic><topic>Cell Proliferation</topic><topic>Cells, Cultured</topic><topic>Female</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation - genetics</topic><topic>Gene Expression Regulation - physiology</topic><topic>Green Fluorescent Proteins - genetics</topic><topic>Green Fluorescent Proteins - metabolism</topic><topic>Homeodomain Proteins - genetics</topic><topic>Homeodomain Proteins - metabolism</topic><topic>Humans</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Transgenic</topic><topic>Nerve Tissue Proteins - metabolism</topic><topic>Neurons - physiology</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Prosencephalon - cytology</topic><topic>Rats</topic><topic>RNA, Messenger - metabolism</topic><topic>RNA, Small Interfering - metabolism</topic><topic>SOXB1 Transcription Factors - metabolism</topic><topic>Transfection</topic><topic>Two-Hybrid System Techniques</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shimozaki, Koji</creatorcontrib><creatorcontrib>Clemenson, Jr, Gregory D</creatorcontrib><creatorcontrib>Gage, Fred H</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shimozaki, Koji</au><au>Clemenson, Jr, Gregory D</au><au>Gage, Fred H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Paired related homeobox protein 1 is a regulator of stemness in adult neural stem/progenitor cells</atitle><jtitle>The Journal of neuroscience</jtitle><addtitle>J Neurosci</addtitle><date>2013-02-27</date><risdate>2013</risdate><volume>33</volume><issue>9</issue><spage>4066</spage><epage>4075</epage><pages>4066-4075</pages><issn>0270-6474</issn><issn>1529-2401</issn><eissn>1529-2401</eissn><abstract>Newborn neurons are generated from neural stem cells (NSCs) in two major niches of the adult brain. Maintenance of self-renewal and multipotency of adult NSCs is controlled by multiple transcription factor networks. We show here that paired related homeobox protein Prx1 (MHox1/Prrx1) plays an important role in the maintenance of adult NSCs. Prx1 works with the transcription factor Sox2 as a coactivator, and depletion of Prx1 in cultured adult mouse NSCs reduces their self-renewal. In addition, we find that Prx1 protein is expressed in Sox2(+)/GFAP(+)/Nestin(+) astrocytes in the germinal regions of the adult mouse forebrain. The continuous expression of Prx1 in proliferating adult mouse hippocampal stem/progenitor cells in vivo leads to the generation of radial/horizontal-shaped astrocyte progenitor- and oligodendrocyte progenitor-like cells with no newborn neurons in the neurogenic niche. These data suggest that Prx1 plays an important role as a key switch for neural cell lineage determination and the maintenance of the self-renewal of adult NSCs at several stages in the adult brain.</abstract><cop>United States</cop><pub>Society for Neuroscience</pub><pmid>23447615</pmid><doi>10.1523/JNEUROSCI.4586-12.2013</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Adult Stem Cells - physiology Animals Astrocytes - physiology Bromodeoxyuridine Caspase 3 - metabolism Cell Differentiation - genetics Cell Proliferation Cells, Cultured Female Gene Expression Profiling Gene Expression Regulation - genetics Gene Expression Regulation - physiology Green Fluorescent Proteins - genetics Green Fluorescent Proteins - metabolism Homeodomain Proteins - genetics Homeodomain Proteins - metabolism Humans Mice Mice, Inbred C57BL Mice, Transgenic Nerve Tissue Proteins - metabolism Neurons - physiology Oligonucleotide Array Sequence Analysis Prosencephalon - cytology Rats RNA, Messenger - metabolism RNA, Small Interfering - metabolism SOXB1 Transcription Factors - metabolism Transfection Two-Hybrid System Techniques |
| title | Paired related homeobox protein 1 is a regulator of stemness in adult neural stem/progenitor cells |
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