Defining the earliest step of cardiovascular lineage segregation by single-cell RNA-seq

Fabienne Lescroart, Xiaonan Wang, Xionghui Lin, Benjamin Swedlund, Souhir Gargouri, Adriana Sànchez-Dànes, Victoria Moignard, Christine Dubois, Catherine Paulissen, Sarah Kinston, Berthold Göttgens, Cédric Blanpain

Science 10.1126. (25 January 2018): eaao4174.

Mouse heart development arises from Mesp1 expressing cardiovascular progenitors (CPs) that are specified during gastrulation. The molecular processes that control early regional and lineage segregation of CPs have been unclear. Here, we performed single cell RNA-sequencing of WT and Mesp1 null CPs in mice. We showed that populations of Mesp1 CPs are molecularly distinct and span the continuum between epiblast and later mesodermal cells including hematopoietic progenitors. Single cell transcriptome analysis of Mesp1-deficient CPs showed that Mesp1 is required for the exit from the pluripotent state and the induction of the cardiovascular gene expression program. We identified distinct populations of Mesp1 CPs that correspond to progenitors committed to different cell lineages and regions of the heart, identifying the molecular features associated with early lineage restriction and regional segregation of the heart at the early stage of mouse gastrulation.