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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Veröffentlicht in:PloS one 2017-03, Vol.12 (3), p.e0173047
Hauptverfasser: 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
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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. 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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 - 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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 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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.</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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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