TY - JOUR T1 - Single-cell transcriptional regulations and accessible chromatin landscape of cell fate decisions in early heart development JF - bioRxiv DO - 10.1101/210930 SP - 210930 AU - Guangshuai Jia AU - Jens Preussner AU - Stefan Guenther AU - Xuejun Yuan AU - Michail Yekelchyk AU - Carsten Kuenne AU - Mario Looso AU - Yonggang Zhou AU - Thomas Braun Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/10/29/210930.abstract N2 - Formation and segregation of the cell lineages forming the vertebrate heart have been studied extensively by genetic cell tracing techniques and by analysis of single marker gene expression both in embryos and differentiating ES cells. However, the underlying gene regulatory networks driving cell fate transitions during early cardiogenesis is only partially understood, in part due to limited cell numbers and substantial cellular heterogeneity within the early embryo. Here, we comprehensively characterized cardiac progenitor cells (CPC) marked by Nkx2-5 and Isl1 expression from embryonic days E7.5 to E9.5 using single-cell RNA sequencing. By leveraging on cell-to-cell heterogeneity, we identified different previously unknown cardiac sub-populations. Reconstruction of the developmental trajectory revealed that Isl1+ CPC represent a transitional cell population maintaining a prolonged multipotent state, whereas extended expression of Nkx-2.5 commits CPC to a unidirectional cardiomyocyte fate. Correlation-based analysis of cells in the unstable multipotent state uncovered underlying gene regulatory networks associated with differentiation. Furthermore, we show that CPC fate transitions are associated with distinct open chromatin states, which critically depend on Isl1 for accessibility of enhancers. In contrast, forced expression of Nkx2-5 eliminated multipotency of Isl1+ cells and established a unidirectional cardiomyocyte fate. Our data provides a transcriptional map for early cardiogenic events at single-cell resolution and establishes a general model of transcriptional and epigenetic regulations during cardiac progenitor cell fate decisions. ER -