DNA Methylation Dynamics in Human Induced Pluripotent Stem Cells over Time

Epigenetic reprogramming is a critical event in the generation of induced pluripotent stem cells (iPSCs). Here, we determined the DNA methylation profiles of 22 human iPSC lines derived from five different cell types (human endometrium, placental artery endothelium, amnion, fetal lung fibroblast, an...

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Main Authors:	Nishino, Koichiro, Toyoda, Masashi, Yamazaki-Inoue, Mayu, Fukawatase, Yoshihiro, Chikazawa, Emi, Sakaguchi, Hironari, Akutsu, Hidenori, Umezawa, Akihiro
Format:	Online
Language:	English
Published:	Public Library of Science 2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3102737/

id	pubmed-3102737
recordtype	oai_dc
spelling	pubmed-31027372011-06-02 DNA Methylation Dynamics in Human Induced Pluripotent Stem Cells over Time Nishino, Koichiro Toyoda, Masashi Yamazaki-Inoue, Mayu Fukawatase, Yoshihiro Chikazawa, Emi Sakaguchi, Hironari Akutsu, Hidenori Umezawa, Akihiro Research Article Epigenetic reprogramming is a critical event in the generation of induced pluripotent stem cells (iPSCs). Here, we determined the DNA methylation profiles of 22 human iPSC lines derived from five different cell types (human endometrium, placental artery endothelium, amnion, fetal lung fibroblast, and menstrual blood cell) and five human embryonic stem cell (ESC) lines, and we followed the aberrant methylation sites in iPSCs for up to 42 weeks. The iPSCs exhibited distinct epigenetic differences from ESCs, which were caused by aberrant methylation at early passages. Multiple appearances and then disappearances of random aberrant methylation were detected throughout iPSC reprogramming. Continuous passaging of the iPSCs diminished the differences between iPSCs and ESCs, implying that iPSCs lose the characteristics inherited from the parent cells and adapt to very closely resemble ESCs over time. Human iPSCs were gradually reprogrammed through the “convergence” of aberrant hyper-methylation events that continuously appeared in a de novo manner. This iPS reprogramming consisted of stochastic de novo methylation and selection/fixation of methylation in an environment suitable for ESCs. Taken together, random methylation and convergence are driving forces for long-term reprogramming of iPSCs to ESCs. Public Library of Science 2011-05-26 /pmc/articles/PMC3102737/ /pubmed/21637780 http://dx.doi.org/10.1371/journal.pgen.1002085 Text en Nishino et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Nishino, Koichiro Toyoda, Masashi Yamazaki-Inoue, Mayu Fukawatase, Yoshihiro Chikazawa, Emi Sakaguchi, Hironari Akutsu, Hidenori Umezawa, Akihiro
spellingShingle	Nishino, Koichiro Toyoda, Masashi Yamazaki-Inoue, Mayu Fukawatase, Yoshihiro Chikazawa, Emi Sakaguchi, Hironari Akutsu, Hidenori Umezawa, Akihiro DNA Methylation Dynamics in Human Induced Pluripotent Stem Cells over Time
author_facet	Nishino, Koichiro Toyoda, Masashi Yamazaki-Inoue, Mayu Fukawatase, Yoshihiro Chikazawa, Emi Sakaguchi, Hironari Akutsu, Hidenori Umezawa, Akihiro
author_sort	Nishino, Koichiro
title	DNA Methylation Dynamics in Human Induced Pluripotent Stem Cells over Time
title_short	DNA Methylation Dynamics in Human Induced Pluripotent Stem Cells over Time
title_full	DNA Methylation Dynamics in Human Induced Pluripotent Stem Cells over Time
title_fullStr	DNA Methylation Dynamics in Human Induced Pluripotent Stem Cells over Time
title_full_unstemmed	DNA Methylation Dynamics in Human Induced Pluripotent Stem Cells over Time
title_sort	dna methylation dynamics in human induced pluripotent stem cells over time
description	Epigenetic reprogramming is a critical event in the generation of induced pluripotent stem cells (iPSCs). Here, we determined the DNA methylation profiles of 22 human iPSC lines derived from five different cell types (human endometrium, placental artery endothelium, amnion, fetal lung fibroblast, and menstrual blood cell) and five human embryonic stem cell (ESC) lines, and we followed the aberrant methylation sites in iPSCs for up to 42 weeks. The iPSCs exhibited distinct epigenetic differences from ESCs, which were caused by aberrant methylation at early passages. Multiple appearances and then disappearances of random aberrant methylation were detected throughout iPSC reprogramming. Continuous passaging of the iPSCs diminished the differences between iPSCs and ESCs, implying that iPSCs lose the characteristics inherited from the parent cells and adapt to very closely resemble ESCs over time. Human iPSCs were gradually reprogrammed through the “convergence” of aberrant hyper-methylation events that continuously appeared in a de novo manner. This iPS reprogramming consisted of stochastic de novo methylation and selection/fixation of methylation in an environment suitable for ESCs. Taken together, random methylation and convergence are driving forces for long-term reprogramming of iPSCs to ESCs.
publisher	Public Library of Science
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3102737/
_version_	1611455979397840896

DNA Methylation Dynamics in Human Induced Pluripotent Stem Cells over Time

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