Kyohei Fujita    Department   Research Institutes and Facilities, Research Institutes and Facilities    Position   Assistant Professor (Fixed Term)
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	Association of Human iPSC Gene Signatures and X Chromosome Dosage with Two Distinct Cardiac Differentiation Trajectories.
Journal	Formal name：Stem cell reports Abbreviation：Stem Cell Reports ISSN code：22136711/22136711
Domestic / Foregin	Foregin
Volume, Issue, Page	13(5),pp.924-938
Author and coauthor	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
Publication date	2019/11
Summary	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