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

Abstract

Mouse heart development arises from <i>Mesp1</i>-expressing cardiovascular progenitors (CPs) that are specified during gastrulation. The molecular processes that control early regional and lineage segregation of CPs have been unclear. We performed single-cell RNA sequencing of wild-type and <i>Mesp1</i>-null CPs in mice. We showed that populations of <i>Mesp1</i> CPs are molecularly distinct and span the continuum between epiblast and later mesodermal cells, including hematopoietic progenitors. Single-cell transcriptome analysis of <i>Mesp1</i>-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 <i>Mesp1</i> 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.