フジタ　キヨウヘイ   Fujita Kiyouhei   藤田　恭平    所属   医学部 医学科    職種   助教
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Association of Human iPSC Gene Signatures and X Chromosome Dosage with Two Distinct Cardiac Differentiation Trajectories.
掲載誌名	正式名：Stem cell reports 略　 称：Stem Cell Reports ISSNコード：22136711/22136711
掲載区分	国外
巻・号・頁	13(5),pp.924-938
著者・共著者	D'Antonio-Chronowska Agnieszka, Donovan Margaret K R, Young Greenwald William W, Nguyen Jennifer Phuong, Fujita Kyohei, Hashem Sherin, Matsui Hiroko, Soncin Francesca, Parast Mana, Ward Michelle C, Coulet Florence, Smith Erin N, Adler Eric, D'Antonio Matteo, Frazer Kelly A
発行年月	2019/11
概要	Despite the importance of understanding how variability across induced pluripotent stem cell (iPSC) lines due to non-genetic factors (clone and passage) influences their differentiation outcome, large-scale studies capable of addressing this question have not yet been conducted. Here, we differentiated 191 iPSC lines to generate iPSC-derived cardiovascular progenitor cells (iPSC-CVPCs). We observed cellular heterogeneity across the iPSC-CVPC samples due to varying fractions of two cell types: cardiomyocytes (CMs) and epicardium-derived cells (EPDCs). Comparing the transcriptomes of CM-fated and EPDC-fated iPSCs, we discovered that 91 signature genes and X chromosome dosage differences are associated with these two distinct cardiac developmental trajectories. In an independent set of 39 iPSCs differentiated into CMs, we confirmed that sex and transcriptional differences affect cardiac-fate outcome. Our study provides novel insights into how iPSC transcriptional and X chromosome gene dosage differences influence their response to differentiation stimuli and, hence, cardiac cell fate.
DOI	10.1016/j.stemcr.2019.09.011
PMID	31668852