Complementary patterns of gene expression by human oligodendrocyte progenitors and their environment predict determinants of progenitor maintenance and differentiation
Objective Glial progenitor cells are abundant in adult human white matter. This study was designed to identify signaling pathways regulating their self‐renewal and fate. Methods We compared the transcriptional profiles of freshly sorted adult human white matter progenitor cells (WMPCs), purified by...
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| Veröffentlicht in: | Annals of neurology 2006-05, Vol.59 (5), p.763-779 |
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| container_title | Annals of neurology |
| container_volume | 59 |
| creator | Sim, Fraser J. Lang, Jennifer K. Waldau, Ben Roy, Neeta S. Schwartz, Theodore E. Pilcher, Webster H. Chandross, Karen J. Natesan, Sridaran Merrill, Jean E. Goldmanm, Steven A. |
| description | Objective
Glial progenitor cells are abundant in adult human white matter. This study was designed to identify signaling pathways regulating their self‐renewal and fate.
Methods
We compared the transcriptional profiles of freshly sorted adult human white matter progenitor cells (WMPCs), purified by A2B5‐based immunomagnetic sorting, with those of the white matter from which they derived.
Results
We identified 132 genes differentially expressed by WMPCs; these included principal components of five receptor‐defined signaling pathways, represented by platelet derived growth factor receptor alpha (PDGFRA) and type 3 fibroblast growth factor receptor (FGFR3), receptor tyrosine phosphatase‐β/ζ (RTPZ), notch, and syndecan3. WMPCs also differentially expressed the bone morphogenetic protein 4 (BMP4) inhibitors neuralin and BAMBI (BMP and activin membrane‐bound inhibitor), suggesting tonic defense against BMP signaling. Differential overexpression of RTPZ was accompanied by that of its modulators pleiotrophin, NrCAM, tenascin, and the chondroitin sulfate proteoglycans, suggesting the importance of RTPZ signaling to WMPCs. When exposed to the RTPZ inhibitor bpV(phen), or lentiviral‐shRNAi against RTPZ, WMPCs differentiated as oligodendrocytes. Conversely, when neuralin and BAMBI were antagonized by BMP4, astrocytic differentiation was induced, which was reversible by noggin.
Interpretation
The RTPZ and BMP pathways regulate the self‐maintenance of adult human WMPCs, and can be modulated to induce their oligodendrocytic or astrocytic differentiation. As such, they provide targets by which to productively mobilize resident progenitor cells of the adult human brain. Ann Neurol 2006;59:763–779 |
| doi_str_mv | 10.1002/ana.20812 |
| format | Article |
| fullrecord | <record><control><sourceid>wiley_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1002_ana_20812</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>ANA20812</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3602-8cb14270bb28eb7c94215299e9e260245a94ee650b81d36a08b16bff2a36072d3</originalsourceid><addsrcrecordid>eNp1kM1uEzEUhS0EoqGw4AWQNyxYTOu_8cwso6ikSFFgAUJiY9njO61hxh7ZLjRP1NesmwSyYuXF_b5z5IPQW0ouKCHsUnt9wUhL2TO0oDWnVctE9xwtCJeiqikXZ-hVSj8JIZ2k5CU6o1JyQQRboIdVmOYRJvBZxx2edc4QfcJhwDfgAcP9HCElFzw2O3x7N2mPw-huggVvY-h3GfAcQ2FdDjFh7S3Ot-AiBv_bxeCfkgsB1vUZWyjpk_Pa533FycSTdj5DufSwD7FuGCAW2elc2l-jF4MeE7w5vufo28err6vravN5_Wm13FQ9l4RVbW-oYA0xhrVgmr4TjNas66ADVu6i1p0AkDUxLbVcatIaKs0wMF30hll-jj4ccvsYUoowqDm6qUyjKFFPY6syttqPXdh3B3a-MxPYE3lctwDvj4BOvR6HWH7n0olrmrrllBfu8sD9cSPs_t-oltvl3-rqYLiU4f6foeMvJRve1Or7dq22P0jdfNms1TV_BKyPqhs</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Complementary patterns of gene expression by human oligodendrocyte progenitors and their environment predict determinants of progenitor maintenance and differentiation</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Sim, Fraser J. ; Lang, Jennifer K. ; Waldau, Ben ; Roy, Neeta S. ; Schwartz, Theodore E. ; Pilcher, Webster H. ; Chandross, Karen J. ; Natesan, Sridaran ; Merrill, Jean E. ; Goldmanm, Steven A.</creator><creatorcontrib>Sim, Fraser J. ; Lang, Jennifer K. ; Waldau, Ben ; Roy, Neeta S. ; Schwartz, Theodore E. ; Pilcher, Webster H. ; Chandross, Karen J. ; Natesan, Sridaran ; Merrill, Jean E. ; Goldmanm, Steven A.</creatorcontrib><description>Objective
Glial progenitor cells are abundant in adult human white matter. This study was designed to identify signaling pathways regulating their self‐renewal and fate.
Methods
We compared the transcriptional profiles of freshly sorted adult human white matter progenitor cells (WMPCs), purified by A2B5‐based immunomagnetic sorting, with those of the white matter from which they derived.
Results
We identified 132 genes differentially expressed by WMPCs; these included principal components of five receptor‐defined signaling pathways, represented by platelet derived growth factor receptor alpha (PDGFRA) and type 3 fibroblast growth factor receptor (FGFR3), receptor tyrosine phosphatase‐β/ζ (RTPZ), notch, and syndecan3. WMPCs also differentially expressed the bone morphogenetic protein 4 (BMP4) inhibitors neuralin and BAMBI (BMP and activin membrane‐bound inhibitor), suggesting tonic defense against BMP signaling. Differential overexpression of RTPZ was accompanied by that of its modulators pleiotrophin, NrCAM, tenascin, and the chondroitin sulfate proteoglycans, suggesting the importance of RTPZ signaling to WMPCs. When exposed to the RTPZ inhibitor bpV(phen), or lentiviral‐shRNAi against RTPZ, WMPCs differentiated as oligodendrocytes. Conversely, when neuralin and BAMBI were antagonized by BMP4, astrocytic differentiation was induced, which was reversible by noggin.
Interpretation
The RTPZ and BMP pathways regulate the self‐maintenance of adult human WMPCs, and can be modulated to induce their oligodendrocytic or astrocytic differentiation. As such, they provide targets by which to productively mobilize resident progenitor cells of the adult human brain. Ann Neurol 2006;59:763–779</description><identifier>ISSN: 0364-5134</identifier><identifier>EISSN: 1531-8249</identifier><identifier>DOI: 10.1002/ana.20812</identifier><identifier>PMID: 16634042</identifier><identifier>CODEN: ANNED3</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Adolescent ; Adult ; Biological and medical sciences ; Bone Morphogenetic Proteins - genetics ; Bone Morphogenetic Proteins - physiology ; Carrier Proteins - genetics ; Carrier Proteins - pharmacology ; Cell Adhesion Molecules - biosynthesis ; Cell Differentiation - physiology ; Cytokines - pharmacology ; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases ; Environment ; Extracellular Matrix Proteins - biosynthesis ; Extracellular Matrix Proteins - genetics ; Female ; Gene Expression - physiology ; Human viral diseases ; Humans ; Immunohistochemistry ; Infectious diseases ; Lentivirus - metabolism ; Male ; Medical sciences ; Middle Aged ; Neurology ; Oligodendroglia - physiology ; Oligonucleotide Array Sequence Analysis ; Protein Tyrosine Phosphatases - metabolism ; Receptors, Cell Surface - drug effects ; Receptors, Notch - genetics ; Receptors, Notch - physiology ; Reverse Transcriptase Polymerase Chain Reaction ; RNA - biosynthesis ; RNA - isolation & purification ; RNA, Small Interfering - pharmacology ; Signal Transduction - physiology ; Stem Cells - physiology ; Viral diseases ; Viral diseases of the lymphoid tissue and the blood. Aids</subject><ispartof>Annals of neurology, 2006-05, Vol.59 (5), p.763-779</ispartof><rights>Copyright © 2006 American Neurological Association</rights><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3602-8cb14270bb28eb7c94215299e9e260245a94ee650b81d36a08b16bff2a36072d3</citedby><cites>FETCH-LOGICAL-c3602-8cb14270bb28eb7c94215299e9e260245a94ee650b81d36a08b16bff2a36072d3</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%2Fana.20812$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fana.20812$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,778,782,1414,27911,27912,45561,45562</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17758313$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16634042$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sim, Fraser J.</creatorcontrib><creatorcontrib>Lang, Jennifer K.</creatorcontrib><creatorcontrib>Waldau, Ben</creatorcontrib><creatorcontrib>Roy, Neeta S.</creatorcontrib><creatorcontrib>Schwartz, Theodore E.</creatorcontrib><creatorcontrib>Pilcher, Webster H.</creatorcontrib><creatorcontrib>Chandross, Karen J.</creatorcontrib><creatorcontrib>Natesan, Sridaran</creatorcontrib><creatorcontrib>Merrill, Jean E.</creatorcontrib><creatorcontrib>Goldmanm, Steven A.</creatorcontrib><title>Complementary patterns of gene expression by human oligodendrocyte progenitors and their environment predict determinants of progenitor maintenance and differentiation</title><title>Annals of neurology</title><addtitle>Ann Neurol</addtitle><description>Objective
Glial progenitor cells are abundant in adult human white matter. This study was designed to identify signaling pathways regulating their self‐renewal and fate.
Methods
We compared the transcriptional profiles of freshly sorted adult human white matter progenitor cells (WMPCs), purified by A2B5‐based immunomagnetic sorting, with those of the white matter from which they derived.
Results
We identified 132 genes differentially expressed by WMPCs; these included principal components of five receptor‐defined signaling pathways, represented by platelet derived growth factor receptor alpha (PDGFRA) and type 3 fibroblast growth factor receptor (FGFR3), receptor tyrosine phosphatase‐β/ζ (RTPZ), notch, and syndecan3. WMPCs also differentially expressed the bone morphogenetic protein 4 (BMP4) inhibitors neuralin and BAMBI (BMP and activin membrane‐bound inhibitor), suggesting tonic defense against BMP signaling. Differential overexpression of RTPZ was accompanied by that of its modulators pleiotrophin, NrCAM, tenascin, and the chondroitin sulfate proteoglycans, suggesting the importance of RTPZ signaling to WMPCs. When exposed to the RTPZ inhibitor bpV(phen), or lentiviral‐shRNAi against RTPZ, WMPCs differentiated as oligodendrocytes. Conversely, when neuralin and BAMBI were antagonized by BMP4, astrocytic differentiation was induced, which was reversible by noggin.
Interpretation
The RTPZ and BMP pathways regulate the self‐maintenance of adult human WMPCs, and can be modulated to induce their oligodendrocytic or astrocytic differentiation. As such, they provide targets by which to productively mobilize resident progenitor cells of the adult human brain. Ann Neurol 2006;59:763–779</description><subject>Adolescent</subject><subject>Adult</subject><subject>Biological and medical sciences</subject><subject>Bone Morphogenetic Proteins - genetics</subject><subject>Bone Morphogenetic Proteins - physiology</subject><subject>Carrier Proteins - genetics</subject><subject>Carrier Proteins - pharmacology</subject><subject>Cell Adhesion Molecules - biosynthesis</subject><subject>Cell Differentiation - physiology</subject><subject>Cytokines - pharmacology</subject><subject>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</subject><subject>Environment</subject><subject>Extracellular Matrix Proteins - biosynthesis</subject><subject>Extracellular Matrix Proteins - genetics</subject><subject>Female</subject><subject>Gene Expression - physiology</subject><subject>Human viral diseases</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Infectious diseases</subject><subject>Lentivirus - metabolism</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Neurology</subject><subject>Oligodendroglia - physiology</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Protein Tyrosine Phosphatases - metabolism</subject><subject>Receptors, Cell Surface - drug effects</subject><subject>Receptors, Notch - genetics</subject><subject>Receptors, Notch - physiology</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA - biosynthesis</subject><subject>RNA - isolation & purification</subject><subject>RNA, Small Interfering - pharmacology</subject><subject>Signal Transduction - physiology</subject><subject>Stem Cells - physiology</subject><subject>Viral diseases</subject><subject>Viral diseases of the lymphoid tissue and the blood. Aids</subject><issn>0364-5134</issn><issn>1531-8249</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kM1uEzEUhS0EoqGw4AWQNyxYTOu_8cwso6ikSFFgAUJiY9njO61hxh7ZLjRP1NesmwSyYuXF_b5z5IPQW0ouKCHsUnt9wUhL2TO0oDWnVctE9xwtCJeiqikXZ-hVSj8JIZ2k5CU6o1JyQQRboIdVmOYRJvBZxx2edc4QfcJhwDfgAcP9HCElFzw2O3x7N2mPw-huggVvY-h3GfAcQ2FdDjFh7S3Ot-AiBv_bxeCfkgsB1vUZWyjpk_Pa533FycSTdj5DufSwD7FuGCAW2elc2l-jF4MeE7w5vufo28err6vravN5_Wm13FQ9l4RVbW-oYA0xhrVgmr4TjNas66ADVu6i1p0AkDUxLbVcatIaKs0wMF30hll-jj4ccvsYUoowqDm6qUyjKFFPY6syttqPXdh3B3a-MxPYE3lctwDvj4BOvR6HWH7n0olrmrrllBfu8sD9cSPs_t-oltvl3-rqYLiU4f6foeMvJRve1Or7dq22P0jdfNms1TV_BKyPqhs</recordid><startdate>200605</startdate><enddate>200605</enddate><creator>Sim, Fraser J.</creator><creator>Lang, Jennifer K.</creator><creator>Waldau, Ben</creator><creator>Roy, Neeta S.</creator><creator>Schwartz, Theodore E.</creator><creator>Pilcher, Webster H.</creator><creator>Chandross, Karen J.</creator><creator>Natesan, Sridaran</creator><creator>Merrill, Jean E.</creator><creator>Goldmanm, Steven A.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Willey-Liss</general><scope>BSCLL</scope><scope>IQODW</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></search><sort><creationdate>200605</creationdate><title>Complementary patterns of gene expression by human oligodendrocyte progenitors and their environment predict determinants of progenitor maintenance and differentiation</title><author>Sim, Fraser J. ; Lang, Jennifer K. ; Waldau, Ben ; Roy, Neeta S. ; Schwartz, Theodore E. ; Pilcher, Webster H. ; Chandross, Karen J. ; Natesan, Sridaran ; Merrill, Jean E. ; Goldmanm, Steven A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3602-8cb14270bb28eb7c94215299e9e260245a94ee650b81d36a08b16bff2a36072d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Biological and medical sciences</topic><topic>Bone Morphogenetic Proteins - genetics</topic><topic>Bone Morphogenetic Proteins - physiology</topic><topic>Carrier Proteins - genetics</topic><topic>Carrier Proteins - pharmacology</topic><topic>Cell Adhesion Molecules - biosynthesis</topic><topic>Cell Differentiation - physiology</topic><topic>Cytokines - pharmacology</topic><topic>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</topic><topic>Environment</topic><topic>Extracellular Matrix Proteins - biosynthesis</topic><topic>Extracellular Matrix Proteins - genetics</topic><topic>Female</topic><topic>Gene Expression - physiology</topic><topic>Human viral diseases</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Infectious diseases</topic><topic>Lentivirus - metabolism</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Neurology</topic><topic>Oligodendroglia - physiology</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Protein Tyrosine Phosphatases - metabolism</topic><topic>Receptors, Cell Surface - drug effects</topic><topic>Receptors, Notch - genetics</topic><topic>Receptors, Notch - physiology</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA - biosynthesis</topic><topic>RNA - isolation & purification</topic><topic>RNA, Small Interfering - pharmacology</topic><topic>Signal Transduction - physiology</topic><topic>Stem Cells - physiology</topic><topic>Viral diseases</topic><topic>Viral diseases of the lymphoid tissue and the blood. Aids</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sim, Fraser J.</creatorcontrib><creatorcontrib>Lang, Jennifer K.</creatorcontrib><creatorcontrib>Waldau, Ben</creatorcontrib><creatorcontrib>Roy, Neeta S.</creatorcontrib><creatorcontrib>Schwartz, Theodore E.</creatorcontrib><creatorcontrib>Pilcher, Webster H.</creatorcontrib><creatorcontrib>Chandross, Karen J.</creatorcontrib><creatorcontrib>Natesan, Sridaran</creatorcontrib><creatorcontrib>Merrill, Jean E.</creatorcontrib><creatorcontrib>Goldmanm, Steven A.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Annals of neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sim, Fraser J.</au><au>Lang, Jennifer K.</au><au>Waldau, Ben</au><au>Roy, Neeta S.</au><au>Schwartz, Theodore E.</au><au>Pilcher, Webster H.</au><au>Chandross, Karen J.</au><au>Natesan, Sridaran</au><au>Merrill, Jean E.</au><au>Goldmanm, Steven A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Complementary patterns of gene expression by human oligodendrocyte progenitors and their environment predict determinants of progenitor maintenance and differentiation</atitle><jtitle>Annals of neurology</jtitle><addtitle>Ann Neurol</addtitle><date>2006-05</date><risdate>2006</risdate><volume>59</volume><issue>5</issue><spage>763</spage><epage>779</epage><pages>763-779</pages><issn>0364-5134</issn><eissn>1531-8249</eissn><coden>ANNED3</coden><abstract>Objective
Glial progenitor cells are abundant in adult human white matter. This study was designed to identify signaling pathways regulating their self‐renewal and fate.
Methods
We compared the transcriptional profiles of freshly sorted adult human white matter progenitor cells (WMPCs), purified by A2B5‐based immunomagnetic sorting, with those of the white matter from which they derived.
Results
We identified 132 genes differentially expressed by WMPCs; these included principal components of five receptor‐defined signaling pathways, represented by platelet derived growth factor receptor alpha (PDGFRA) and type 3 fibroblast growth factor receptor (FGFR3), receptor tyrosine phosphatase‐β/ζ (RTPZ), notch, and syndecan3. WMPCs also differentially expressed the bone morphogenetic protein 4 (BMP4) inhibitors neuralin and BAMBI (BMP and activin membrane‐bound inhibitor), suggesting tonic defense against BMP signaling. Differential overexpression of RTPZ was accompanied by that of its modulators pleiotrophin, NrCAM, tenascin, and the chondroitin sulfate proteoglycans, suggesting the importance of RTPZ signaling to WMPCs. When exposed to the RTPZ inhibitor bpV(phen), or lentiviral‐shRNAi against RTPZ, WMPCs differentiated as oligodendrocytes. Conversely, when neuralin and BAMBI were antagonized by BMP4, astrocytic differentiation was induced, which was reversible by noggin.
Interpretation
The RTPZ and BMP pathways regulate the self‐maintenance of adult human WMPCs, and can be modulated to induce their oligodendrocytic or astrocytic differentiation. As such, they provide targets by which to productively mobilize resident progenitor cells of the adult human brain. Ann Neurol 2006;59:763–779</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>16634042</pmid><doi>10.1002/ana.20812</doi><tpages>17</tpages></addata></record> |
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| ispartof | Annals of neurology, 2006-05, Vol.59 (5), p.763-779 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Adolescent Adult Biological and medical sciences Bone Morphogenetic Proteins - genetics Bone Morphogenetic Proteins - physiology Carrier Proteins - genetics Carrier Proteins - pharmacology Cell Adhesion Molecules - biosynthesis Cell Differentiation - physiology Cytokines - pharmacology Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Environment Extracellular Matrix Proteins - biosynthesis Extracellular Matrix Proteins - genetics Female Gene Expression - physiology Human viral diseases Humans Immunohistochemistry Infectious diseases Lentivirus - metabolism Male Medical sciences Middle Aged Neurology Oligodendroglia - physiology Oligonucleotide Array Sequence Analysis Protein Tyrosine Phosphatases - metabolism Receptors, Cell Surface - drug effects Receptors, Notch - genetics Receptors, Notch - physiology Reverse Transcriptase Polymerase Chain Reaction RNA - biosynthesis RNA - isolation & purification RNA, Small Interfering - pharmacology Signal Transduction - physiology Stem Cells - physiology Viral diseases Viral diseases of the lymphoid tissue and the blood. Aids |
| title | Complementary patterns of gene expression by human oligodendrocyte progenitors and their environment predict determinants of progenitor maintenance and differentiation |
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