Hypoxia induces re‐entry of committed cells into pluripotency
ABSTRACT Adult stem cells reside in hypoxic niches, and embryonic stem cells (ESCs) are derived from a low oxygen environment. However, it is not clear whether hypoxia is critical for stem cell fate since for example human ESCs (hESCs) are able to self‐renew in atmospheric oxygen concentrations as w...
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Veröffentlicht in: | Stem cells (Dayton, Ohio) Ohio), 2013-09, Vol.31 (9), p.1737-1748 |
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creator | Mathieu, Julie Zhang, Zhan Nelson, Angelique Lamba, Deepak A. Reh, Thomas A. Ware, Carol Ruohola‐Baker, Hannele |
description | ABSTRACT
Adult stem cells reside in hypoxic niches, and embryonic stem cells (ESCs) are derived from a low oxygen environment. However, it is not clear whether hypoxia is critical for stem cell fate since for example human ESCs (hESCs) are able to self‐renew in atmospheric oxygen concentrations as well. We now show that hypoxia can govern cell fate decisions since hypoxia alone can revert hESC‐ or iPSC‐derived differentiated cells back to a stem cell‐like state, as evidenced by re‐activation of an Oct4‐promoter reporter. Hypoxia‐induced “de‐differentiated” cells also mimic hESCs in their morphology, long‐term self‐renewal capacity, genome‐wide mRNA and miRNA profiles, Oct4 promoter methylation state, cell surface markers TRA1–60 and SSEA4 expression, and capacity to form teratomas. These data demonstrate that hypoxia can influence cell fate decisions and could elucidate hypoxic niche function. Stem Cells 2013;31:1737‐1748 |
doi_str_mv | 10.1002/stem.1446 |
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Adult stem cells reside in hypoxic niches, and embryonic stem cells (ESCs) are derived from a low oxygen environment. However, it is not clear whether hypoxia is critical for stem cell fate since for example human ESCs (hESCs) are able to self‐renew in atmospheric oxygen concentrations as well. We now show that hypoxia can govern cell fate decisions since hypoxia alone can revert hESC‐ or iPSC‐derived differentiated cells back to a stem cell‐like state, as evidenced by re‐activation of an Oct4‐promoter reporter. Hypoxia‐induced “de‐differentiated” cells also mimic hESCs in their morphology, long‐term self‐renewal capacity, genome‐wide mRNA and miRNA profiles, Oct4 promoter methylation state, cell surface markers TRA1–60 and SSEA4 expression, and capacity to form teratomas. These data demonstrate that hypoxia can influence cell fate decisions and could elucidate hypoxic niche function. Stem Cells 2013;31:1737‐1748</description><identifier>ISSN: 1066-5099</identifier><identifier>EISSN: 1549-4918</identifier><identifier>DOI: 10.1002/stem.1446</identifier><identifier>PMID: 23765801</identifier><language>eng</language><publisher>United States: Oxford University Press</publisher><subject>Adult ; Animals ; Basic Helix-Loop-Helix Transcription Factors - metabolism ; Biomarkers - metabolism ; Cell Dedifferentiation - drug effects ; Cell Hypoxia - drug effects ; Cell Line ; Cell Lineage - drug effects ; dedifferentiation ; Embryonic Stem Cells - cytology ; Embryonic Stem Cells - drug effects ; Embryonic Stem Cells - metabolism ; Embryos ; Green Fluorescent Proteins - metabolism ; hESC ; Histone Deacetylases - metabolism ; Human embryonic stem cell ; Humans ; Hypoxia ; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism ; Mice ; Models, Biological ; niche ; Octamer Transcription Factor-3 - metabolism ; Oxygen - pharmacology ; Plasticity ; Pluripotent Stem Cells - cytology ; Pluripotent Stem Cells - drug effects ; Pluripotent Stem Cells - metabolism ; Stem cell fate ; Stem cells</subject><ispartof>Stem cells (Dayton, Ohio), 2013-09, Vol.31 (9), p.1737-1748</ispartof><rights>AlphaMed Press</rights><rights>AlphaMed Press.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4766-e6c244c1466ad66fcd1b67b5bb686c89d47616bd6c5036ac2fd384e048ba478e3</citedby><cites>FETCH-LOGICAL-c4766-e6c244c1466ad66fcd1b67b5bb686c89d47616bd6c5036ac2fd384e048ba478e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23765801$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mathieu, Julie</creatorcontrib><creatorcontrib>Zhang, Zhan</creatorcontrib><creatorcontrib>Nelson, Angelique</creatorcontrib><creatorcontrib>Lamba, Deepak A.</creatorcontrib><creatorcontrib>Reh, Thomas A.</creatorcontrib><creatorcontrib>Ware, Carol</creatorcontrib><creatorcontrib>Ruohola‐Baker, Hannele</creatorcontrib><title>Hypoxia induces re‐entry of committed cells into pluripotency</title><title>Stem cells (Dayton, Ohio)</title><addtitle>Stem Cells</addtitle><description>ABSTRACT
Adult stem cells reside in hypoxic niches, and embryonic stem cells (ESCs) are derived from a low oxygen environment. However, it is not clear whether hypoxia is critical for stem cell fate since for example human ESCs (hESCs) are able to self‐renew in atmospheric oxygen concentrations as well. We now show that hypoxia can govern cell fate decisions since hypoxia alone can revert hESC‐ or iPSC‐derived differentiated cells back to a stem cell‐like state, as evidenced by re‐activation of an Oct4‐promoter reporter. Hypoxia‐induced “de‐differentiated” cells also mimic hESCs in their morphology, long‐term self‐renewal capacity, genome‐wide mRNA and miRNA profiles, Oct4 promoter methylation state, cell surface markers TRA1–60 and SSEA4 expression, and capacity to form teratomas. These data demonstrate that hypoxia can influence cell fate decisions and could elucidate hypoxic niche function. Stem Cells 2013;31:1737‐1748</description><subject>Adult</subject><subject>Animals</subject><subject>Basic Helix-Loop-Helix Transcription Factors - metabolism</subject><subject>Biomarkers - metabolism</subject><subject>Cell Dedifferentiation - drug effects</subject><subject>Cell Hypoxia - drug effects</subject><subject>Cell Line</subject><subject>Cell Lineage - drug effects</subject><subject>dedifferentiation</subject><subject>Embryonic Stem Cells - cytology</subject><subject>Embryonic Stem Cells - drug effects</subject><subject>Embryonic Stem Cells - metabolism</subject><subject>Embryos</subject><subject>Green Fluorescent Proteins - metabolism</subject><subject>hESC</subject><subject>Histone Deacetylases - metabolism</subject><subject>Human embryonic stem cell</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>Hypoxia-Inducible Factor 1, alpha Subunit - metabolism</subject><subject>Mice</subject><subject>Models, Biological</subject><subject>niche</subject><subject>Octamer Transcription Factor-3 - metabolism</subject><subject>Oxygen - pharmacology</subject><subject>Plasticity</subject><subject>Pluripotent Stem Cells - cytology</subject><subject>Pluripotent Stem Cells - drug effects</subject><subject>Pluripotent Stem Cells - metabolism</subject><subject>Stem cell fate</subject><subject>Stem cells</subject><issn>1066-5099</issn><issn>1549-4918</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kctKxDAUhoMoXkYXvoAU3OhinKS5NN0oMowXGHGhrkOaphppm5q0anc-gs_ok5g6Kiq4OoHz8fGf_ABsI3iAIIwnvtXVASKELYF1REk6Jiniy-ENGRtTmKZrYMP7ewgRoZyvgrUYJ4xyiNbB0Vnf2GcjI1PnndI-cvrt5VXXresjW0TKVpVpW51HSpelD1Rro6bsnGlsq2vVb4KVQpZeb33OEbg5mV1Pz8bzy9Pz6fF8rEgSQmimYkIUIozJnLFC5ShjSUazjHGmeJoHCrEsZ4pCzKSKixxzoiHhmSQJ13gEDhfepssqnashoSxF40wlXS-sNOL3pjZ34tY-CpzGCCY0CPY-Bc4-dNq3ojJ-OErW2nZehO_DOOEYpwHd_YPe287V4bxABR-nNCaB2l9QylnvnS6-wyAohlrEUMvgZYHd-Zn-m_zqIQCTBfBkSt3_bxJX17OLD-U7yCaZWw</recordid><startdate>201309</startdate><enddate>201309</enddate><creator>Mathieu, Julie</creator><creator>Zhang, Zhan</creator><creator>Nelson, Angelique</creator><creator>Lamba, Deepak A.</creator><creator>Reh, Thomas A.</creator><creator>Ware, Carol</creator><creator>Ruohola‐Baker, Hannele</creator><general>Oxford University Press</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>7QO</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>201309</creationdate><title>Hypoxia induces re‐entry of committed cells into pluripotency</title><author>Mathieu, Julie ; 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Adult stem cells reside in hypoxic niches, and embryonic stem cells (ESCs) are derived from a low oxygen environment. However, it is not clear whether hypoxia is critical for stem cell fate since for example human ESCs (hESCs) are able to self‐renew in atmospheric oxygen concentrations as well. We now show that hypoxia can govern cell fate decisions since hypoxia alone can revert hESC‐ or iPSC‐derived differentiated cells back to a stem cell‐like state, as evidenced by re‐activation of an Oct4‐promoter reporter. Hypoxia‐induced “de‐differentiated” cells also mimic hESCs in their morphology, long‐term self‐renewal capacity, genome‐wide mRNA and miRNA profiles, Oct4 promoter methylation state, cell surface markers TRA1–60 and SSEA4 expression, and capacity to form teratomas. These data demonstrate that hypoxia can influence cell fate decisions and could elucidate hypoxic niche function. Stem Cells 2013;31:1737‐1748</abstract><cop>United States</cop><pub>Oxford University Press</pub><pmid>23765801</pmid><doi>10.1002/stem.1446</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adult Animals Basic Helix-Loop-Helix Transcription Factors - metabolism Biomarkers - metabolism Cell Dedifferentiation - drug effects Cell Hypoxia - drug effects Cell Line Cell Lineage - drug effects dedifferentiation Embryonic Stem Cells - cytology Embryonic Stem Cells - drug effects Embryonic Stem Cells - metabolism Embryos Green Fluorescent Proteins - metabolism hESC Histone Deacetylases - metabolism Human embryonic stem cell Humans Hypoxia Hypoxia-Inducible Factor 1, alpha Subunit - metabolism Mice Models, Biological niche Octamer Transcription Factor-3 - metabolism Oxygen - pharmacology Plasticity Pluripotent Stem Cells - cytology Pluripotent Stem Cells - drug effects Pluripotent Stem Cells - metabolism Stem cell fate Stem cells |
title | Hypoxia induces re‐entry of committed cells into pluripotency |
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