RT Journal Article
SR Electronic
T1 Analysis of cardiac differentiation at single cell resolution reveals a requirement of hypertrophic signaling for HOPX transcription
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 229294
DO 10.1101/229294
A1 Clayton E Friedman
A1 Quan Nguyen
A1 Samuel W Lukowski
A1 Han Sheng Chiu
A1 Abbigail Helfer
A1 Jason Miklas
A1 Shengbao Suo Suo
A1 Jing-Dong Jackie Han
A1 Pierre Osteil
A1 Guangdun Peng
A1 Naihe Jing
A1 Greg J Baillie
A1 Anne Senabouth
A1 Angelika N Christ
A1 Timothy J Bruxner
A1 Charles E Murry
A1 Emily S Wong
A1 Jun Ding
A1 Yuliang Wang
A1 James Hudson
A1 Hannele Ruohola-Baker
A1 Ziv Bar-Joseph
A1 Patrick P L Tam
A1 Joseph E Powell
A1 Nathan J Palpant
YR 2018
UL http://biorxiv.org/content/early/2018/06/20/229294.abstract
AB Differentiation into diverse cell lineages requires the orchestration of gene regulatory networks guiding diverse cell fate choices. Utilizing human pluripotent stem cells, we measured expression dynamics of 17,718 genes from 43,168 cells across five time points over a thirty day time-course of in vitro cardiac-directed differentiation. Unsupervised clustering and lineage prediction algorithms were used to map fate choices and transcriptional networks underlying cardiac differentiation. We leveraged this resource to identify strategies for controlling in vitro differentiation as it occurs in vivo. HOPX, a non-DNA binding homeodomain protein essential for heart development in vivo was identified as dys-regulated in in vitro derived cardiomyocytes. Utilizing genetic gain and loss of function approaches, we dissect the transcriptional complexity of the HOPX locus and identify the requirement of hypertrophic signaling for HOPX transcription in hPSC-derived cardiomyocytes. This work provides a single cell dissection of the transcriptional landscape of cardiac differentiation for broad applications of stem cells in cardiovascular biology.