Analysis of cardiac differentiation at single cell resolution reveals a requirement of hypertrophic signaling for HOPX transcription

• DOI: 10.1101/229294
• Publication Date: 2017-12-08T06:10:23Z
• Authors: Clayton E Friedman; Quan Nguyen; Samuel W Lukowski; Han Sheng Chiu; Abbigail Helfer; Jason Miklas; Shengbao Suo Suo; Jing-Dong Jackie Han; Pierre Osteil; Guangdun Peng; Naihe Jing; Greg J Baillie; Anne Senabouth; Angelika N Christ; Timothy J Bruxner; Charles E Murry; Emily S Wong; Jun Ding; Yuliang Wang; James Hudson; Hannele Ruohola-B...; Ziv Bar-Joseph; Patrick P L Tam; Joseph E Powell; Nathan J Palpant
• Keywords: Gene regulatory network; Cell fate determination; Directed differentiation

Abstract Differentiation into diverse cell lineages requires the orchestration of gene regulatory networks guiding fate choices. Utilizing human pluripotent stem cells, we measured expression dynamics 17,718 genes from 43,168 cells across five time points over a thirty day time-course in vitro cardiac-directed differentiation. Unsupervised clustering and lineage prediction algorithms were used to map choices transcriptional underlying cardiac We leveraged this resource identify strategies for controlling differentiation as it occurs vivo . HOPX, non-DNA binding homeodomain protein essential heart development was identified dys-regulated derived cardiomyocytes. genetic gain loss function approaches, dissect complexity HOPX locus requirement hypertrophic signaling transcription hPSC-derived This work provides single dissection landscape broad applications cardiovascular biology.