Epigenetic Enzymes, Age, and Ancestry Regulate the Efficiency of Human iPSC Reprogramming

Stem Cells
Lantz C MackeyTrevor K Archer

Abstract

Epigenetic enzymes regulate higher-order chromatin architecture and cell-type specific gene expression. The ATPase BRG1 and the SWI/SNF chromatin remodeling complex are epigenetic enzymes that regulate chromatin accessibility during steady and transitional cell states. Experiments in mice show that the loss of BRG1 inhibits cellular reprogramming, while studies using human cells demonstrate that the overexpression of BRG1 enhances reprogramming. We hypothesized that the variation of SWI/SNF subunit expression in the human population would contribute to variability in the efficiency of induced pluripotent stem cells (iPSC) reprogramming. To examine the impact of an individual's sex, ancestry, and age on iPSC reprogramming, we created a novel sex and ancestry balanced cohort of 240 iPSC lines derived from human dermal fibroblasts (DF) from 80 heathy donors. We methodically assessed the reprogramming efficiency of each DF line and then quantified the individual and demographic-specific variations in SWI/SNF chromatin remodeling proteins and mRNA expression. We identified BRG1, BAF155, and BAF60a expression as strongly correlating with iPSC reprogramming efficiency. Additionally, we discovered that high efficiency iPSC reprograming...Continue Reading

References

Dec 17, 2004·Genes & Development·Zhong WangRobert Tjian
Dec 7, 2007·Nature Biotechnology·Masato NakagawaShinya Yamanaka
Feb 28, 2008·Nuclear Receptor Signaling·Kevin W Trotter, Trevor K Archer
Mar 13, 2009·Proceedings of the National Academy of Sciences of the United States of America·Lena HoGerald R Crabtree
Mar 13, 2009·Proceedings of the National Academy of Sciences of the United States of America·Lena HoGerald R Crabtree
Aug 12, 2009·Nature·Han LiManuel Serrano
Jun 17, 2010·Cell·Nishant SinghalHans R Schöler
Jul 21, 2010·Nature·K KimG Q Daley
Oct 15, 2010·Journal of Cellular Physiology·Ritchie HoKathrin Plath
Jan 8, 2011·Cell Stem Cell·Richard P KocheAlexander Meissner
Jan 14, 2011·Journal of Molecular Cell Biology·Zhao ChengKen-Ichi Isobe
Mar 2, 2011·Cell Research·Diana C Hargreaves, Gerald R Crabtree
Mar 6, 2012·Nature·Tamer T OnderGeorge Q Daley
Nov 14, 2012·Current Opinion in Cell Biology·Salah Mahmoudi, Anne Brunet
May 30, 2013·Development·Kazutoshi Takahashi, Shinya Yamanaka
Aug 22, 2013·Biogerontology·Phetcharat PhanthongAndras Dinnyes
Oct 25, 2013·Nature·Effie Apostolou, Konrad Hochedlinger
Nov 19, 2013·Cell Cycle·Francesco FerrariKonrad Hochedlinger
Aug 7, 2014·Proceedings of the National Academy of Sciences of the United States of America·Mari OhnukiKazutoshi Takahashi
Jun 10, 2015·Molecular and Cellular Biology·Kevin W TrotterTrevor K Archer
Nov 13, 2015·Critical Reviews in Eukaryotic Gene Expression·Chenxia Hu, Lan-Juan Li
Jan 29, 2016·Nature Reviews. Molecular Cell Biology·Yishai AviorNissim Benvenisty
Feb 18, 2016·Nature Reviews. Molecular Cell Biology·Kazutoshi Takahashi, Shinya Yamanaka
Feb 26, 2016·Nature Reviews. Molecular Cell Biology·Alan Trounson, Natalie D DeWitt
Jul 19, 2016·Nucleus·Monica TyagiAshok K Patel
Dec 17, 2016·Nature Reviews. Drug Discovery·Yanhong ShiShinya Yamanaka
Mar 23, 2017·Cell Reports·Amrita M NargundJames J Hsieh
Jan 27, 2014·Biomedicines·Aaron Shaw, Kenneth Cornetta
Aug 22, 2017·Current Opinion in Genetics & Development·Yixuan WangShaorong Gao

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Citations

Nov 15, 2018·Stem Cells·Julie R Beegle
Dec 13, 2018·Current Drug Targets·Xiaotong WangYe Yuan
Jun 13, 2020·Frontiers in Cell and Developmental Biology·Anna SlanziGabriela Constantin
Sep 26, 2020·Frontiers in Cellular Neuroscience·Jonathan EintrachtMariya Moosajee
Jul 25, 2021·International Journal of Molecular Sciences·Jacob ReissMasatoshi Suzuki
Nov 1, 2021·Toxicological Sciences : an Official Journal of the Society of Toxicology·Emma C BowersShaun D McCullough

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