DNA repair and replication links to pluripotency and differentiation capacity of pig iPS cells
Pigs are proposed to be suitable large animal models for test of the efficacy and safety of induced pluripotent stem cells (iPSCs) for stem cell therapy, but authentic pig ES/iPS cell lines with germline competence are rarely produced. The pathways or signaling underlying the defective competent pig...
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creator | Liu, Kai Mao, Jian Song, Lipu Fan, Anran Zhang, Sheng Wang, Jianyu Fan, Nana Liu, Na Ye, Xiaoying Fu, Haifeng Zhou, Zhongcheng Wang, Yong Wei, Hong Liu, Zhonghua Li, Ziyi Lai, Liangxue Wang, Xumin Liu, Lin |
description | Pigs are proposed to be suitable large animal models for test of the efficacy and safety of induced pluripotent stem cells (iPSCs) for stem cell therapy, but authentic pig ES/iPS cell lines with germline competence are rarely produced. The pathways or signaling underlying the defective competent pig iPSCs remain poorly understood. By improving induction conditions using various small chemicals, we generated pig iPSCs that exhibited high pluripotency and differentiation capacity that can contribute to chimeras. However, their potency was reduced with increasing passages by teratoma formation test, and correlated with declined expression levels of Rex1, an important marker for naïve state. By RNA-sequencing analysis, genes related to WNT signaling were upregulated and MAPK signaling and TGFβ pathways downregulated in pig iPSCs compared to fibroblasts, but they were abnormally expressed during passages. Notably, pathways involving in DNA repair and replication were upregulated at early passage, but downregulated in iPSCs during prolonged passage in cluster with fibroblasts. Our data suggests that reduced DNA repair and replication capacity links to the instability of pig iPSCs. Targeting these pathways may facilitate generation of truly pluripotent pig iPSCs, with implication in translational studies. |
doi_str_mv | 10.1371/journal.pone.0173047 |
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The pathways or signaling underlying the defective competent pig iPSCs remain poorly understood. By improving induction conditions using various small chemicals, we generated pig iPSCs that exhibited high pluripotency and differentiation capacity that can contribute to chimeras. However, their potency was reduced with increasing passages by teratoma formation test, and correlated with declined expression levels of Rex1, an important marker for naïve state. By RNA-sequencing analysis, genes related to WNT signaling were upregulated and MAPK signaling and TGFβ pathways downregulated in pig iPSCs compared to fibroblasts, but they were abnormally expressed during passages. Notably, pathways involving in DNA repair and replication were upregulated at early passage, but downregulated in iPSCs during prolonged passage in cluster with fibroblasts. Our data suggests that reduced DNA repair and replication capacity links to the instability of pig iPSCs. Targeting these pathways may facilitate generation of truly pluripotent pig iPSCs, with implication in translational studies.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0173047</identifier><identifier>PMID: 28253351</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Animal models ; Animals ; Biology ; Biology and Life Sciences ; Cell Differentiation ; Cell lines ; Chimeras ; Collaboration ; Deoxyribonucleic acid ; Differentiation ; DNA ; DNA biosynthesis ; DNA methylation ; DNA Repair ; DNA Replication ; Embryonic stem cells ; Epigenetics ; Fibroblasts ; Gene expression ; Gene sequencing ; Genomics ; Health aspects ; Hogs ; Hospitals ; Induced Pluripotent Stem Cells - cytology ; Laboratories ; Life sciences ; MAP kinase ; MAP Kinase Signaling System ; Medicine and Health Sciences ; Mice ; Physical Sciences ; Pigs ; Pluripotency ; Quality ; Repair ; Replication ; Ribonucleic acid ; RNA ; Signal transduction ; Signaling ; Stability ; Stem cell transplantation ; Stem cells ; Swine ; Teratoma ; Wnt protein</subject><ispartof>PloS one, 2017-03, Vol.12 (3), p.e0173047</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://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>2017 Liu et al 2017 Liu et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c791t-c3b46c4f080018185108675b46ee1363cae38c762e8d26dcb22a20b02e0bbf223</citedby><cites>FETCH-LOGICAL-c791t-c3b46c4f080018185108675b46ee1363cae38c762e8d26dcb22a20b02e0bbf223</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/PMC5333863/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5333863/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2103,2929,23871,27929,27930,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28253351$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Cooney, Austin John</contributor><creatorcontrib>Liu, Kai</creatorcontrib><creatorcontrib>Mao, Jian</creatorcontrib><creatorcontrib>Song, Lipu</creatorcontrib><creatorcontrib>Fan, Anran</creatorcontrib><creatorcontrib>Zhang, Sheng</creatorcontrib><creatorcontrib>Wang, Jianyu</creatorcontrib><creatorcontrib>Fan, Nana</creatorcontrib><creatorcontrib>Liu, Na</creatorcontrib><creatorcontrib>Ye, Xiaoying</creatorcontrib><creatorcontrib>Fu, Haifeng</creatorcontrib><creatorcontrib>Zhou, Zhongcheng</creatorcontrib><creatorcontrib>Wang, Yong</creatorcontrib><creatorcontrib>Wei, Hong</creatorcontrib><creatorcontrib>Liu, Zhonghua</creatorcontrib><creatorcontrib>Li, Ziyi</creatorcontrib><creatorcontrib>Lai, Liangxue</creatorcontrib><creatorcontrib>Wang, Xumin</creatorcontrib><creatorcontrib>Liu, Lin</creatorcontrib><title>DNA repair and replication links to pluripotency and differentiation capacity of pig iPS cells</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Pigs are proposed to be suitable large animal models for test of the efficacy and safety of induced pluripotent stem cells (iPSCs) for stem cell therapy, but authentic pig ES/iPS cell lines with germline competence are rarely produced. The pathways or signaling underlying the defective competent pig iPSCs remain poorly understood. By improving induction conditions using various small chemicals, we generated pig iPSCs that exhibited high pluripotency and differentiation capacity that can contribute to chimeras. However, their potency was reduced with increasing passages by teratoma formation test, and correlated with declined expression levels of Rex1, an important marker for naïve state. By RNA-sequencing analysis, genes related to WNT signaling were upregulated and MAPK signaling and TGFβ pathways downregulated in pig iPSCs compared to fibroblasts, but they were abnormally expressed during passages. Notably, pathways involving in DNA repair and replication were upregulated at early passage, but downregulated in iPSCs during prolonged passage in cluster with fibroblasts. Our data suggests that reduced DNA repair and replication capacity links to the instability of pig iPSCs. Targeting these pathways may facilitate generation of truly pluripotent pig iPSCs, with implication in translational studies.</description><subject>Analysis</subject><subject>Animal models</subject><subject>Animals</subject><subject>Biology</subject><subject>Biology and Life Sciences</subject><subject>Cell Differentiation</subject><subject>Cell lines</subject><subject>Chimeras</subject><subject>Collaboration</subject><subject>Deoxyribonucleic acid</subject><subject>Differentiation</subject><subject>DNA</subject><subject>DNA biosynthesis</subject><subject>DNA methylation</subject><subject>DNA Repair</subject><subject>DNA Replication</subject><subject>Embryonic stem cells</subject><subject>Epigenetics</subject><subject>Fibroblasts</subject><subject>Gene expression</subject><subject>Gene sequencing</subject><subject>Genomics</subject><subject>Health aspects</subject><subject>Hogs</subject><subject>Hospitals</subject><subject>Induced Pluripotent Stem Cells - cytology</subject><subject>Laboratories</subject><subject>Life sciences</subject><subject>MAP kinase</subject><subject>MAP Kinase Signaling System</subject><subject>Medicine and Health Sciences</subject><subject>Mice</subject><subject>Physical Sciences</subject><subject>Pigs</subject><subject>Pluripotency</subject><subject>Quality</subject><subject>Repair</subject><subject>Replication</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Signal transduction</subject><subject>Signaling</subject><subject>Stability</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Swine</subject><subject>Teratoma</subject><subject>Wnt protein</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</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>eNqNk11v0zAUhiMEYmPwDxBEQkJw0eKPxHZuJlXjq9LEEAMusRzHaV1cO9gOov8ep82mBu0C5SLW8XPeY78-J8ueQjCHmMI3G9d7K8y8c1bNAaQYFPRedgorjGYEAXz_aH2SPQphA0CJGSEPsxPEUIlxCU-zH28_LXKvOqF9LmwzLI2WImpnc6Ptz5BHl3em97pzUVm521ONblvllY36QErRCanjLndt3ulVrj9f51IZEx5nD1phgnoy_s-yb-_ffb34OLu8-rC8WFzOJK1gnElcF0QWLWAAQAZZCQEjtExBpSAmWAqFmaQEKdYg0sgaIYFADZACdd0ihM-y5wfdzrjAR2sCh4xiUgEKWCKWB6JxYsM7r7fC77gTmu8Dzq-48FFLo3iVqtUYNijZVKCqrZgsIEVlKQhMe2XSOh-r9fVWNTIZ4YWZiE53rF7zlfvNk-npBXASeDUKePerVyHyrQ6DYcIq1-_PTVNtgEhCX_yD3n27kVqJdAFtW5fqykGULwqGaVFVGCZqfgeVvkZttUx91OoUnyS8niQkJqo_cSX6EPjy-sv_s1ffp-zLI3athInr4Ew_NFOYgsUBlN6F4FV7azIEfBiDGzf4MAZ8HIOU9uz4gW6Tbvoe_wXNUgET</recordid><startdate>20170302</startdate><enddate>20170302</enddate><creator>Liu, 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repair and replication links to pluripotency and differentiation capacity of pig iPS cells</title><author>Liu, Kai ; Mao, Jian ; Song, Lipu ; Fan, Anran ; Zhang, Sheng ; Wang, Jianyu ; Fan, Nana ; Liu, Na ; Ye, Xiaoying ; Fu, Haifeng ; Zhou, Zhongcheng ; Wang, Yong ; Wei, Hong ; Liu, Zhonghua ; Li, Ziyi ; Lai, Liangxue ; Wang, Xumin ; Liu, Lin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c791t-c3b46c4f080018185108675b46ee1363cae38c762e8d26dcb22a20b02e0bbf223</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Analysis</topic><topic>Animal models</topic><topic>Animals</topic><topic>Biology</topic><topic>Biology and Life Sciences</topic><topic>Cell Differentiation</topic><topic>Cell lines</topic><topic>Chimeras</topic><topic>Collaboration</topic><topic>Deoxyribonucleic acid</topic><topic>Differentiation</topic><topic>DNA</topic><topic>DNA biosynthesis</topic><topic>DNA methylation</topic><topic>DNA Repair</topic><topic>DNA Replication</topic><topic>Embryonic stem cells</topic><topic>Epigenetics</topic><topic>Fibroblasts</topic><topic>Gene expression</topic><topic>Gene sequencing</topic><topic>Genomics</topic><topic>Health aspects</topic><topic>Hogs</topic><topic>Hospitals</topic><topic>Induced Pluripotent Stem Cells - cytology</topic><topic>Laboratories</topic><topic>Life sciences</topic><topic>MAP kinase</topic><topic>MAP Kinase Signaling System</topic><topic>Medicine and Health Sciences</topic><topic>Mice</topic><topic>Physical Sciences</topic><topic>Pigs</topic><topic>Pluripotency</topic><topic>Quality</topic><topic>Repair</topic><topic>Replication</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>Signal transduction</topic><topic>Signaling</topic><topic>Stability</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>Swine</topic><topic>Teratoma</topic><topic>Wnt 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John</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>DNA repair and replication links to pluripotency and differentiation capacity of pig iPS cells</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2017-03-02</date><risdate>2017</risdate><volume>12</volume><issue>3</issue><spage>e0173047</spage><pages>e0173047-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Pigs are proposed to be suitable large animal models for test of the efficacy and safety of induced pluripotent stem cells (iPSCs) for stem cell therapy, but authentic pig ES/iPS cell lines with germline competence are rarely produced. The pathways or signaling underlying the defective competent pig iPSCs remain poorly understood. By improving induction conditions using various small chemicals, we generated pig iPSCs that exhibited high pluripotency and differentiation capacity that can contribute to chimeras. However, their potency was reduced with increasing passages by teratoma formation test, and correlated with declined expression levels of Rex1, an important marker for naïve state. By RNA-sequencing analysis, genes related to WNT signaling were upregulated and MAPK signaling and TGFβ pathways downregulated in pig iPSCs compared to fibroblasts, but they were abnormally expressed during passages. Notably, pathways involving in DNA repair and replication were upregulated at early passage, but downregulated in iPSCs during prolonged passage in cluster with fibroblasts. Our data suggests that reduced DNA repair and replication capacity links to the instability of pig iPSCs. Targeting these pathways may facilitate generation of truly pluripotent pig iPSCs, with implication in translational studies.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28253351</pmid><doi>10.1371/journal.pone.0173047</doi><tpages>e0173047</tpages><oa>free_for_read</oa></addata></record> |
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source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
subjects | Analysis Animal models Animals Biology Biology and Life Sciences Cell Differentiation Cell lines Chimeras Collaboration Deoxyribonucleic acid Differentiation DNA DNA biosynthesis DNA methylation DNA Repair DNA Replication Embryonic stem cells Epigenetics Fibroblasts Gene expression Gene sequencing Genomics Health aspects Hogs Hospitals Induced Pluripotent Stem Cells - cytology Laboratories Life sciences MAP kinase MAP Kinase Signaling System Medicine and Health Sciences Mice Physical Sciences Pigs Pluripotency Quality Repair Replication Ribonucleic acid RNA Signal transduction Signaling Stability Stem cell transplantation Stem cells Swine Teratoma Wnt protein |
title | DNA repair and replication links to pluripotency and differentiation capacity of pig iPS cells |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-14T09%3A05%3A20IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=DNA%20repair%20and%20replication%20links%20to%20pluripotency%20and%20differentiation%20capacity%20of%20pig%20iPS%20cells&rft.jtitle=PloS%20one&rft.au=Liu,%20Kai&rft.date=2017-03-02&rft.volume=12&rft.issue=3&rft.spage=e0173047&rft.pages=e0173047-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0173047&rft_dat=%3Cgale_plos_%3EA483749931%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1873690708&rft_id=info:pmid/28253351&rft_galeid=A483749931&rft_doaj_id=oai_doaj_org_article_9ae3b31d2282429f98c417255a619ae5&rfr_iscdi=true |