Cord blood administration induces oligodendrocyte survival through alterations in gene expression
Abstract Oligodendrocytes (OLs), the predominant cell type found in cerebral white matter, are essential for structural integrity and proper neural signaling. Very little is known concerning stroke-induced OL dysfunction. Our laboratory has shown that infusion of human umbilical cord blood (HUCB) ce...
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| Veröffentlicht in: | Brain research 2010-12, Vol.1366, p.172-188 |
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| creator | Rowe, D.D Leonardo, C.C Hall, A.A Shahaduzzaman, M.D Collier, L.A Willing, A.E Pennypacker, K.R |
| description | Abstract Oligodendrocytes (OLs), the predominant cell type found in cerebral white matter, are essential for structural integrity and proper neural signaling. Very little is known concerning stroke-induced OL dysfunction. Our laboratory has shown that infusion of human umbilical cord blood (HUCB) cells protects striatal white matter tracts in vivo and directly protects mature primary OL cultures from oxygen glucose deprivation (OGD). Microarray studies of RNA prepared from OL cultures subjected to OGD and treated with HUCB cells showed an increase in the expression of 33 genes associated with OL proliferation, survival, and repair functions, such as myelination. The microarray results were verified using quantitative RT-PCR for the following eight genes: U2AF homology motif kinase 1 ( Uhmk1 ), insulin-induced gene 1 ( Insig1 ), metallothionein 3 ( Mt3 ), tetraspanin 2 ( Tspan2 ), peroxiredoxin 4 ( Prdx4 ), stathmin-like 2 ( Stmn2 ), myelin oligodendrocyte glycoprotein ( MOG ), and versican ( Vcan ). Immunohistochemistry showed that MOG, Prdx4, Uhmk1, Insig1, and Mt3 protein expression were upregulated in the ipsilateral white matter tracts of rats infused with HUCB cells 48 h after middle cerebral artery occlusion (MCAO). Furthermore, promoter region analysis of these genes revealed common transcription factor binding sites, providing insight into the shared signal transduction pathways activated by HUCB cells to enhance transcription of these genes. These results show expression of genes induced by HUCB cell therapy that could confer oligoprotection from ischemia. |
| doi_str_mv | 10.1016/j.brainres.2010.09.078 |
| format | Article |
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Very little is known concerning stroke-induced OL dysfunction. Our laboratory has shown that infusion of human umbilical cord blood (HUCB) cells protects striatal white matter tracts in vivo and directly protects mature primary OL cultures from oxygen glucose deprivation (OGD). Microarray studies of RNA prepared from OL cultures subjected to OGD and treated with HUCB cells showed an increase in the expression of 33 genes associated with OL proliferation, survival, and repair functions, such as myelination. The microarray results were verified using quantitative RT-PCR for the following eight genes: U2AF homology motif kinase 1 ( Uhmk1 ), insulin-induced gene 1 ( Insig1 ), metallothionein 3 ( Mt3 ), tetraspanin 2 ( Tspan2 ), peroxiredoxin 4 ( Prdx4 ), stathmin-like 2 ( Stmn2 ), myelin oligodendrocyte glycoprotein ( MOG ), and versican ( Vcan ). Immunohistochemistry showed that MOG, Prdx4, Uhmk1, Insig1, and Mt3 protein expression were upregulated in the ipsilateral white matter tracts of rats infused with HUCB cells 48 h after middle cerebral artery occlusion (MCAO). Furthermore, promoter region analysis of these genes revealed common transcription factor binding sites, providing insight into the shared signal transduction pathways activated by HUCB cells to enhance transcription of these genes. These results show expression of genes induced by HUCB cell therapy that could confer oligoprotection from ischemia.</description><identifier>ISSN: 0006-8993</identifier><identifier>EISSN: 1872-6240</identifier><identifier>DOI: 10.1016/j.brainres.2010.09.078</identifier><identifier>PMID: 20883670</identifier><identifier>CODEN: BRREAP</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>Animals ; Animals, Newborn ; Anti-oxidant ; Biological and medical sciences ; Cell Proliferation ; Cell Survival - physiology ; Cell- and Tissue-Based Therapy - methods ; Cells, Cultured ; Cerebral Cortex - cytology ; Disease Models, Animal ; Fetal Blood - metabolism ; Gene Expression Profiling - methods ; Gene Expression Regulation - physiology ; Glucose - deficiency ; Human umbilical cord blood cells ; Humans ; Hypoxia ; Infarction, Middle Cerebral Artery - therapy ; Intracellular Signaling Peptides and Proteins - genetics ; Intracellular Signaling Peptides and Proteins - metabolism ; Ischemia ; L-Lactate Dehydrogenase - metabolism ; Medical sciences ; Microarray ; Myelin Proteins - genetics ; Myelin Proteins - metabolism ; Neurology ; O Antigens - metabolism ; Oligodendroglia - drug effects ; Oligodendroglia - physiology ; Oligonucleotide Array Sequence Analysis - methods ; Rats ; Rats, Sprague-Dawley ; Stroke ; Time Factors ; Vascular diseases and vascular malformations of the nervous system ; Versicans - genetics ; Versicans - metabolism ; White matter</subject><ispartof>Brain research, 2010-12, Vol.1366, p.172-188</ispartof><rights>Elsevier B.V.</rights><rights>2010 Elsevier B.V.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2010 Elsevier B.V. All rights reserved.</rights><rights>2010 Elsevier B.V. All rights reserved. 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c587t-6fd35ad4ab55632da2ee6a0bce84f6f94aee6471a8196a029680b61e70bff3333</citedby><cites>FETCH-LOGICAL-c587t-6fd35ad4ab55632da2ee6a0bce84f6f94aee6471a8196a029680b61e70bff3333</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S000689931002144X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23637421$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20883670$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rowe, D.D</creatorcontrib><creatorcontrib>Leonardo, C.C</creatorcontrib><creatorcontrib>Hall, A.A</creatorcontrib><creatorcontrib>Shahaduzzaman, M.D</creatorcontrib><creatorcontrib>Collier, L.A</creatorcontrib><creatorcontrib>Willing, A.E</creatorcontrib><creatorcontrib>Pennypacker, K.R</creatorcontrib><title>Cord blood administration induces oligodendrocyte survival through alterations in gene expression</title><title>Brain research</title><addtitle>Brain Res</addtitle><description>Abstract Oligodendrocytes (OLs), the predominant cell type found in cerebral white matter, are essential for structural integrity and proper neural signaling. Very little is known concerning stroke-induced OL dysfunction. Our laboratory has shown that infusion of human umbilical cord blood (HUCB) cells protects striatal white matter tracts in vivo and directly protects mature primary OL cultures from oxygen glucose deprivation (OGD). Microarray studies of RNA prepared from OL cultures subjected to OGD and treated with HUCB cells showed an increase in the expression of 33 genes associated with OL proliferation, survival, and repair functions, such as myelination. The microarray results were verified using quantitative RT-PCR for the following eight genes: U2AF homology motif kinase 1 ( Uhmk1 ), insulin-induced gene 1 ( Insig1 ), metallothionein 3 ( Mt3 ), tetraspanin 2 ( Tspan2 ), peroxiredoxin 4 ( Prdx4 ), stathmin-like 2 ( Stmn2 ), myelin oligodendrocyte glycoprotein ( MOG ), and versican ( Vcan ). Immunohistochemistry showed that MOG, Prdx4, Uhmk1, Insig1, and Mt3 protein expression were upregulated in the ipsilateral white matter tracts of rats infused with HUCB cells 48 h after middle cerebral artery occlusion (MCAO). Furthermore, promoter region analysis of these genes revealed common transcription factor binding sites, providing insight into the shared signal transduction pathways activated by HUCB cells to enhance transcription of these genes. These results show expression of genes induced by HUCB cell therapy that could confer oligoprotection from ischemia.</description><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Anti-oxidant</subject><subject>Biological and medical sciences</subject><subject>Cell Proliferation</subject><subject>Cell Survival - physiology</subject><subject>Cell- and Tissue-Based Therapy - methods</subject><subject>Cells, Cultured</subject><subject>Cerebral Cortex - cytology</subject><subject>Disease Models, Animal</subject><subject>Fetal Blood - metabolism</subject><subject>Gene Expression Profiling - methods</subject><subject>Gene Expression Regulation - physiology</subject><subject>Glucose - deficiency</subject><subject>Human umbilical cord blood cells</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>Infarction, Middle Cerebral Artery - therapy</subject><subject>Intracellular Signaling Peptides and Proteins - genetics</subject><subject>Intracellular Signaling Peptides and Proteins - metabolism</subject><subject>Ischemia</subject><subject>L-Lactate Dehydrogenase - metabolism</subject><subject>Medical sciences</subject><subject>Microarray</subject><subject>Myelin Proteins - genetics</subject><subject>Myelin Proteins - metabolism</subject><subject>Neurology</subject><subject>O Antigens - metabolism</subject><subject>Oligodendroglia - drug effects</subject><subject>Oligodendroglia - physiology</subject><subject>Oligonucleotide Array Sequence Analysis - methods</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Stroke</subject><subject>Time Factors</subject><subject>Vascular diseases and vascular malformations of the nervous system</subject><subject>Versicans - genetics</subject><subject>Versicans - metabolism</subject><subject>White matter</subject><issn>0006-8993</issn><issn>1872-6240</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUk2P0zAQjRCI7S78hVUuiFPK2E4c57ICVbAgrcQBkLhZjj1pXVy72ElF_z2O2l0-LuuL5fF7bz7eFMU1gSUBwt9sl31U1kdMSwo5CN0SWvGkWBDR0orTGp4WCwDgleg6dlFcprTNT8Y6eF5cUBCC8RYWhVqFaMrehWBKZXbW2zRGNdrgS-vNpDGVwdl1MOhNDPo4YpmmeLAH5cpxE8O03pTKjXjipEwq1-ixxF_7XFvKsRfFs0G5hC_P91Xx7cP7r6uP1d3n20-rd3eVbkQ7VnwwrFGmVn3TcEaNoohcQa9R1AMfulrld90SJUiX47TjAnpOsIV-GFg-V8XNSXc_9Ts0Gn1uxMl9tDsVjzIoK__98XYj1-EgaR6QoDQLvD4LxPBzwjTKnU0anVMew5SkaHjbkpz-cSRpmrphHclIfkLqGFKKODzUQ0DORsqtvDdSzkZK6GQ2MhOv_-7mgXbvXAa8OgNU0soNUXlt0x8c46yt6VzB2xMO8-wPFqNM2qLXaGxEPUoT7OO13PwnoV1elJz1Bx4xbcMUfXZWEpmoBPllXrt56wgAJXX9nf0GGLnYXw</recordid><startdate>20101217</startdate><enddate>20101217</enddate><creator>Rowe, D.D</creator><creator>Leonardo, C.C</creator><creator>Hall, A.A</creator><creator>Shahaduzzaman, M.D</creator><creator>Collier, L.A</creator><creator>Willing, A.E</creator><creator>Pennypacker, K.R</creator><general>Elsevier B.V</general><general>Elsevier</general><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><scope>7X8</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20101217</creationdate><title>Cord blood administration induces oligodendrocyte survival through alterations in gene expression</title><author>Rowe, D.D ; 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Very little is known concerning stroke-induced OL dysfunction. Our laboratory has shown that infusion of human umbilical cord blood (HUCB) cells protects striatal white matter tracts in vivo and directly protects mature primary OL cultures from oxygen glucose deprivation (OGD). Microarray studies of RNA prepared from OL cultures subjected to OGD and treated with HUCB cells showed an increase in the expression of 33 genes associated with OL proliferation, survival, and repair functions, such as myelination. The microarray results were verified using quantitative RT-PCR for the following eight genes: U2AF homology motif kinase 1 ( Uhmk1 ), insulin-induced gene 1 ( Insig1 ), metallothionein 3 ( Mt3 ), tetraspanin 2 ( Tspan2 ), peroxiredoxin 4 ( Prdx4 ), stathmin-like 2 ( Stmn2 ), myelin oligodendrocyte glycoprotein ( MOG ), and versican ( Vcan ). Immunohistochemistry showed that MOG, Prdx4, Uhmk1, Insig1, and Mt3 protein expression were upregulated in the ipsilateral white matter tracts of rats infused with HUCB cells 48 h after middle cerebral artery occlusion (MCAO). Furthermore, promoter region analysis of these genes revealed common transcription factor binding sites, providing insight into the shared signal transduction pathways activated by HUCB cells to enhance transcription of these genes. These results show expression of genes induced by HUCB cell therapy that could confer oligoprotection from ischemia.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>20883670</pmid><doi>10.1016/j.brainres.2010.09.078</doi><tpages>17</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Animals, Newborn Anti-oxidant Biological and medical sciences Cell Proliferation Cell Survival - physiology Cell- and Tissue-Based Therapy - methods Cells, Cultured Cerebral Cortex - cytology Disease Models, Animal Fetal Blood - metabolism Gene Expression Profiling - methods Gene Expression Regulation - physiology Glucose - deficiency Human umbilical cord blood cells Humans Hypoxia Infarction, Middle Cerebral Artery - therapy Intracellular Signaling Peptides and Proteins - genetics Intracellular Signaling Peptides and Proteins - metabolism Ischemia L-Lactate Dehydrogenase - metabolism Medical sciences Microarray Myelin Proteins - genetics Myelin Proteins - metabolism Neurology O Antigens - metabolism Oligodendroglia - drug effects Oligodendroglia - physiology Oligonucleotide Array Sequence Analysis - methods Rats Rats, Sprague-Dawley Stroke Time Factors Vascular diseases and vascular malformations of the nervous system Versicans - genetics Versicans - metabolism White matter |
| title | Cord blood administration induces oligodendrocyte survival through alterations in gene expression |
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