Defining hypo-methylated regions of stem cell-specific promoters in human iPS cells derived from extra-embryonic amnions and lung fibroblasts
Human induced pluripotent stem (iPS) cells are currently used as powerful resources in regenerative medicine. During very early developmental stages, DNA methylation decreases to an overall low level at the blastocyst stage, from which embryonic stem cells are derived. Therefore, pluripotent stem ce...
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| Veröffentlicht in: | PloS one 2010-09, Vol.5 (9), p.e13017-e13017 |
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| creator | Nishino, Koichiro Toyoda, Masashi Yamazaki-Inoue, Mayu Makino, Hatsune Fukawatase, Yoshihiro Chikazawa, Emi Takahashi, Yoriko Miyagawa, Yoshitaka Okita, Hajime Kiyokawa, Nobutaka Akutsu, Hidenori Umezawa, Akihiro |
| description | Human induced pluripotent stem (iPS) cells are currently used as powerful resources in regenerative medicine. During very early developmental stages, DNA methylation decreases to an overall low level at the blastocyst stage, from which embryonic stem cells are derived. Therefore, pluripotent stem cells, such as ES and iPS cells, are considered to have hypo-methylated status compared to differentiated cells. However, epigenetic mechanisms of "stemness" remain unknown in iPS cells derived from extra-embryonic and embryonic cells.
We examined genome-wide DNA methylation (24,949 CpG sites covering 1,3862 genes, mostly selected from promoter regions) with six human iPS cell lines derived from human amniotic cells and fetal lung fibroblasts as well as two human ES cell lines, and eight human differentiated cell lines using Illumina's Infinium HumanMethylation27. A considerable fraction (807 sites) exhibited a distinct difference in the methylation level between the iPS/ES cells and differentiated cells, with 87.6% hyper-methylation seen in iPS/ES cells. However, a limited fraction of CpG sites with hypo-methylation was found in promoters of genes encoding transcription factors. Thus, a group of genes becomes active through a decrease of methylation in their promoters. Twenty-three genes including SOX15, SALL4, TDGF1, PPP1R16B and SOX10 as well as POU5F1 were defined as genes with hypo-methylated SS-DMR (Stem cell-Specific Differentially Methylated Region) and highly expression in iPS/ES cells.
We show that DNA methylation profile of human amniotic iPS cells as well as fibroblast iPS cells, and defined the SS-DMRs. Knowledge of epigenetic information across iPS cells derived from different cell types can be used as a signature for "stemness" and may allow us to screen for optimum iPS/ES cells and to validate and monitor iPS/ES cell derivatives for human therapeutic applications. |
| doi_str_mv | 10.1371/journal.pone.0013017 |
| format | Article |
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We examined genome-wide DNA methylation (24,949 CpG sites covering 1,3862 genes, mostly selected from promoter regions) with six human iPS cell lines derived from human amniotic cells and fetal lung fibroblasts as well as two human ES cell lines, and eight human differentiated cell lines using Illumina's Infinium HumanMethylation27. A considerable fraction (807 sites) exhibited a distinct difference in the methylation level between the iPS/ES cells and differentiated cells, with 87.6% hyper-methylation seen in iPS/ES cells. However, a limited fraction of CpG sites with hypo-methylation was found in promoters of genes encoding transcription factors. Thus, a group of genes becomes active through a decrease of methylation in their promoters. Twenty-three genes including SOX15, SALL4, TDGF1, PPP1R16B and SOX10 as well as POU5F1 were defined as genes with hypo-methylated SS-DMR (Stem cell-Specific Differentially Methylated Region) and highly expression in iPS/ES cells.
We show that DNA methylation profile of human amniotic iPS cells as well as fibroblast iPS cells, and defined the SS-DMRs. Knowledge of epigenetic information across iPS cells derived from different cell types can be used as a signature for "stemness" and may allow us to screen for optimum iPS/ES cells and to validate and monitor iPS/ES cell derivatives for human therapeutic applications.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0013017</identifier><identifier>PMID: 20885964</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Amnion - cytology ; Amnion - metabolism ; Amniotic cells ; Anopheles ; Bioinformatics ; Biotechnology ; Bone marrow ; Cell Differentiation ; Cell Line ; Cell lines ; Cells, Cultured ; Childrens health ; Comparative analysis ; CpG islands ; Deoxyribonucleic acid ; Developmental biology ; Developmental Biology/Stem Cells ; Developmental stages ; DNA ; DNA binding proteins ; DNA Methylation ; Embryo cells ; Embryo fibroblasts ; Embryonic stem cells ; Embryonic Stem Cells - cytology ; Embryonic Stem Cells - metabolism ; Embryos ; Epigenesis, Genetic ; Epigenetic inheritance ; Epigenetics ; Fetuses ; Fibroblasts ; Fibroblasts - cytology ; Fibroblasts - metabolism ; Gene expression ; Genes ; Genetics and Genomics/Epigenetics ; Genomes ; Genomics ; Humans ; Induced Pluripotent Stem Cells - cytology ; Induced Pluripotent Stem Cells - metabolism ; Low level ; Lung - cytology ; Lung - metabolism ; Lungs ; Methylation ; Molecular Biology/Bioinformatics ; Molecular Biology/DNA Methylation ; Muscular dystrophy ; Oct-4 protein ; Pluripotency ; Promoter Regions, Genetic ; Regenerative medicine ; Sox10 protein ; Stem cells ; Therapeutic applications ; Transcription (Genetics) ; Transcription factors ; Transcription Factors - genetics ; Transcription Factors - metabolism</subject><ispartof>PloS one, 2010-09, Vol.5 (9), p.e13017-e13017</ispartof><rights>COPYRIGHT 2010 Public Library of Science</rights><rights>2010 Nishino et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Nishino et al. 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c757t-6191d74a08b7caf41265832f79c55581e8309cf1698af9e4c9d6066b40c2358b3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2946409/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2946409/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53770,53772,79347,79348</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20885964$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Kato, Tadafumi</contributor><creatorcontrib>Nishino, Koichiro</creatorcontrib><creatorcontrib>Toyoda, Masashi</creatorcontrib><creatorcontrib>Yamazaki-Inoue, Mayu</creatorcontrib><creatorcontrib>Makino, Hatsune</creatorcontrib><creatorcontrib>Fukawatase, Yoshihiro</creatorcontrib><creatorcontrib>Chikazawa, Emi</creatorcontrib><creatorcontrib>Takahashi, Yoriko</creatorcontrib><creatorcontrib>Miyagawa, Yoshitaka</creatorcontrib><creatorcontrib>Okita, Hajime</creatorcontrib><creatorcontrib>Kiyokawa, Nobutaka</creatorcontrib><creatorcontrib>Akutsu, Hidenori</creatorcontrib><creatorcontrib>Umezawa, Akihiro</creatorcontrib><title>Defining hypo-methylated regions of stem cell-specific promoters in human iPS cells derived from extra-embryonic amnions and lung fibroblasts</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Human induced pluripotent stem (iPS) cells are currently used as powerful resources in regenerative medicine. During very early developmental stages, DNA methylation decreases to an overall low level at the blastocyst stage, from which embryonic stem cells are derived. Therefore, pluripotent stem cells, such as ES and iPS cells, are considered to have hypo-methylated status compared to differentiated cells. However, epigenetic mechanisms of "stemness" remain unknown in iPS cells derived from extra-embryonic and embryonic cells.
We examined genome-wide DNA methylation (24,949 CpG sites covering 1,3862 genes, mostly selected from promoter regions) with six human iPS cell lines derived from human amniotic cells and fetal lung fibroblasts as well as two human ES cell lines, and eight human differentiated cell lines using Illumina's Infinium HumanMethylation27. A considerable fraction (807 sites) exhibited a distinct difference in the methylation level between the iPS/ES cells and differentiated cells, with 87.6% hyper-methylation seen in iPS/ES cells. However, a limited fraction of CpG sites with hypo-methylation was found in promoters of genes encoding transcription factors. Thus, a group of genes becomes active through a decrease of methylation in their promoters. Twenty-three genes including SOX15, SALL4, TDGF1, PPP1R16B and SOX10 as well as POU5F1 were defined as genes with hypo-methylated SS-DMR (Stem cell-Specific Differentially Methylated Region) and highly expression in iPS/ES cells.
We show that DNA methylation profile of human amniotic iPS cells as well as fibroblast iPS cells, and defined the SS-DMRs. Knowledge of epigenetic information across iPS cells derived from different cell types can be used as a signature for "stemness" and may allow us to screen for optimum iPS/ES cells and to validate and monitor iPS/ES cell derivatives for human therapeutic applications.</description><subject>Amnion - cytology</subject><subject>Amnion - metabolism</subject><subject>Amniotic cells</subject><subject>Anopheles</subject><subject>Bioinformatics</subject><subject>Biotechnology</subject><subject>Bone marrow</subject><subject>Cell Differentiation</subject><subject>Cell Line</subject><subject>Cell lines</subject><subject>Cells, Cultured</subject><subject>Childrens health</subject><subject>Comparative analysis</subject><subject>CpG islands</subject><subject>Deoxyribonucleic acid</subject><subject>Developmental biology</subject><subject>Developmental Biology/Stem Cells</subject><subject>Developmental stages</subject><subject>DNA</subject><subject>DNA binding proteins</subject><subject>DNA Methylation</subject><subject>Embryo cells</subject><subject>Embryo fibroblasts</subject><subject>Embryonic stem cells</subject><subject>Embryonic Stem Cells - cytology</subject><subject>Embryonic Stem Cells - metabolism</subject><subject>Embryos</subject><subject>Epigenesis, Genetic</subject><subject>Epigenetic inheritance</subject><subject>Epigenetics</subject><subject>Fetuses</subject><subject>Fibroblasts</subject><subject>Fibroblasts - cytology</subject><subject>Fibroblasts - metabolism</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Genetics and Genomics/Epigenetics</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Humans</subject><subject>Induced Pluripotent Stem Cells - cytology</subject><subject>Induced Pluripotent Stem Cells - metabolism</subject><subject>Low level</subject><subject>Lung - cytology</subject><subject>Lung - metabolism</subject><subject>Lungs</subject><subject>Methylation</subject><subject>Molecular Biology/Bioinformatics</subject><subject>Molecular Biology/DNA Methylation</subject><subject>Muscular dystrophy</subject><subject>Oct-4 protein</subject><subject>Pluripotency</subject><subject>Promoter Regions, Genetic</subject><subject>Regenerative medicine</subject><subject>Sox10 protein</subject><subject>Stem cells</subject><subject>Therapeutic applications</subject><subject>Transcription (Genetics)</subject><subject>Transcription factors</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk12P1CAUhhujcdfVf2C0iYnGi45AKYUbk836Nckma1z1llB6mGHSQoV24_wI_7PMx25mzF4YLkro874HXjhZ9hyjGS5r_G7lp-BUNxu8gxlCuES4fpCdYlGSghFUPjyYn2RPYlwhVJWcscfZCUGcV4LR0-zPBzDWWbfIl-vBFz2My3WnRmjzAAvrXcy9yeMIfa6h64o4gLbG6nwIvvcjhJhbly-nXrncfr3eQjFvIdibZGESlMPvMagC-iasvUtK1butr3Jt3k2psLFN8E2n4hifZo-M6iI823_Psh-fPn6_-FJcXn2eX5xfFrqu6rFgWOC2pgrxptbKUExYxUtiaqGrquIYeImENpgJrowAqkXLEGMNRZqUFW_Ks-zlznfofJT7JKPERBDKakZoIuY7ovVqJYdgexXW0isrtws-LKQKo9UdSM2rWihFoa0wrY3hhJCSYyUaxSoCJHm931ebmh5aDS4l0h2ZHv9xdikX_kYSQRlFIhm82RsE_2uCOMrexk3UyoGfoqwrxhhlmCXy1T_k_YfbUwuV9m-d8ams3njKc1qX6Tyc8ETN7qHSaKG3Or06Y9P6keDtkSAxY7r9hZpilPPrb__PXv08Zl8fsEtQ3biMvpvGzTs6BukO1MHHGMDcZYyR3DTNbRpy0zRy3zRJ9uLwfu5Et11S_gULqRNq</recordid><startdate>20100927</startdate><enddate>20100927</enddate><creator>Nishino, Koichiro</creator><creator>Toyoda, Masashi</creator><creator>Yamazaki-Inoue, Mayu</creator><creator>Makino, Hatsune</creator><creator>Fukawatase, Yoshihiro</creator><creator>Chikazawa, Emi</creator><creator>Takahashi, Yoriko</creator><creator>Miyagawa, Yoshitaka</creator><creator>Okita, Hajime</creator><creator>Kiyokawa, Nobutaka</creator><creator>Akutsu, Hidenori</creator><creator>Umezawa, Akihiro</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20100927</creationdate><title>Defining hypo-methylated regions of stem cell-specific promoters in human iPS cells derived from extra-embryonic amnions and lung fibroblasts</title><author>Nishino, Koichiro ; Toyoda, Masashi ; Yamazaki-Inoue, Mayu ; Makino, Hatsune ; Fukawatase, Yoshihiro ; Chikazawa, Emi ; Takahashi, Yoriko ; Miyagawa, Yoshitaka ; Okita, Hajime ; Kiyokawa, Nobutaka ; Akutsu, Hidenori ; Umezawa, Akihiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c757t-6191d74a08b7caf41265832f79c55581e8309cf1698af9e4c9d6066b40c2358b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Amnion - 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cytology</topic><topic>Fibroblasts - metabolism</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Genetics and Genomics/Epigenetics</topic><topic>Genomes</topic><topic>Genomics</topic><topic>Humans</topic><topic>Induced Pluripotent Stem Cells - cytology</topic><topic>Induced Pluripotent Stem Cells - metabolism</topic><topic>Low level</topic><topic>Lung - cytology</topic><topic>Lung - metabolism</topic><topic>Lungs</topic><topic>Methylation</topic><topic>Molecular Biology/Bioinformatics</topic><topic>Molecular Biology/DNA Methylation</topic><topic>Muscular dystrophy</topic><topic>Oct-4 protein</topic><topic>Pluripotency</topic><topic>Promoter Regions, Genetic</topic><topic>Regenerative medicine</topic><topic>Sox10 protein</topic><topic>Stem cells</topic><topic>Therapeutic applications</topic><topic>Transcription (Genetics)</topic><topic>Transcription factors</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nishino, Koichiro</creatorcontrib><creatorcontrib>Toyoda, Masashi</creatorcontrib><creatorcontrib>Yamazaki-Inoue, Mayu</creatorcontrib><creatorcontrib>Makino, Hatsune</creatorcontrib><creatorcontrib>Fukawatase, Yoshihiro</creatorcontrib><creatorcontrib>Chikazawa, Emi</creatorcontrib><creatorcontrib>Takahashi, Yoriko</creatorcontrib><creatorcontrib>Miyagawa, Yoshitaka</creatorcontrib><creatorcontrib>Okita, Hajime</creatorcontrib><creatorcontrib>Kiyokawa, Nobutaka</creatorcontrib><creatorcontrib>Akutsu, Hidenori</creatorcontrib><creatorcontrib>Umezawa, Akihiro</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Opposing Viewpoints in Context (Gale)</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Proquest Nursing & Allied Health Source</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nishino, Koichiro</au><au>Toyoda, Masashi</au><au>Yamazaki-Inoue, Mayu</au><au>Makino, Hatsune</au><au>Fukawatase, Yoshihiro</au><au>Chikazawa, Emi</au><au>Takahashi, Yoriko</au><au>Miyagawa, Yoshitaka</au><au>Okita, Hajime</au><au>Kiyokawa, Nobutaka</au><au>Akutsu, Hidenori</au><au>Umezawa, Akihiro</au><au>Kato, Tadafumi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Defining hypo-methylated regions of stem cell-specific promoters in human iPS cells derived from extra-embryonic amnions and lung fibroblasts</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2010-09-27</date><risdate>2010</risdate><volume>5</volume><issue>9</issue><spage>e13017</spage><epage>e13017</epage><pages>e13017-e13017</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Human induced pluripotent stem (iPS) cells are currently used as powerful resources in regenerative medicine. During very early developmental stages, DNA methylation decreases to an overall low level at the blastocyst stage, from which embryonic stem cells are derived. Therefore, pluripotent stem cells, such as ES and iPS cells, are considered to have hypo-methylated status compared to differentiated cells. However, epigenetic mechanisms of "stemness" remain unknown in iPS cells derived from extra-embryonic and embryonic cells.
We examined genome-wide DNA methylation (24,949 CpG sites covering 1,3862 genes, mostly selected from promoter regions) with six human iPS cell lines derived from human amniotic cells and fetal lung fibroblasts as well as two human ES cell lines, and eight human differentiated cell lines using Illumina's Infinium HumanMethylation27. A considerable fraction (807 sites) exhibited a distinct difference in the methylation level between the iPS/ES cells and differentiated cells, with 87.6% hyper-methylation seen in iPS/ES cells. However, a limited fraction of CpG sites with hypo-methylation was found in promoters of genes encoding transcription factors. Thus, a group of genes becomes active through a decrease of methylation in their promoters. Twenty-three genes including SOX15, SALL4, TDGF1, PPP1R16B and SOX10 as well as POU5F1 were defined as genes with hypo-methylated SS-DMR (Stem cell-Specific Differentially Methylated Region) and highly expression in iPS/ES cells.
We show that DNA methylation profile of human amniotic iPS cells as well as fibroblast iPS cells, and defined the SS-DMRs. Knowledge of epigenetic information across iPS cells derived from different cell types can be used as a signature for "stemness" and may allow us to screen for optimum iPS/ES cells and to validate and monitor iPS/ES cell derivatives for human therapeutic applications.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>20885964</pmid><doi>10.1371/journal.pone.0013017</doi><tpages>e13017</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2010-09, Vol.5 (9), p.e13017-e13017 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1292467624 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Amnion - cytology Amnion - metabolism Amniotic cells Anopheles Bioinformatics Biotechnology Bone marrow Cell Differentiation Cell Line Cell lines Cells, Cultured Childrens health Comparative analysis CpG islands Deoxyribonucleic acid Developmental biology Developmental Biology/Stem Cells Developmental stages DNA DNA binding proteins DNA Methylation Embryo cells Embryo fibroblasts Embryonic stem cells Embryonic Stem Cells - cytology Embryonic Stem Cells - metabolism Embryos Epigenesis, Genetic Epigenetic inheritance Epigenetics Fetuses Fibroblasts Fibroblasts - cytology Fibroblasts - metabolism Gene expression Genes Genetics and Genomics/Epigenetics Genomes Genomics Humans Induced Pluripotent Stem Cells - cytology Induced Pluripotent Stem Cells - metabolism Low level Lung - cytology Lung - metabolism Lungs Methylation Molecular Biology/Bioinformatics Molecular Biology/DNA Methylation Muscular dystrophy Oct-4 protein Pluripotency Promoter Regions, Genetic Regenerative medicine Sox10 protein Stem cells Therapeutic applications Transcription (Genetics) Transcription factors Transcription Factors - genetics Transcription Factors - metabolism |
| title | Defining hypo-methylated regions of stem cell-specific promoters in human iPS cells derived from extra-embryonic amnions and lung fibroblasts |
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