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

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Science  09 Mar 2018:
Vol. 359, Issue 6380, pp. 1177-1181
DOI: 10.1126/science.aao4174

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Committing the heart

The heart is a complex organ composed of multiple cell types such as cardiomyocytes and endothelial cells. Cardiovascular cells arise from Mesp1-expressing progenitor cells. Lescroart et al. performed single-cell RNA-sequencing analysis of mouse wild-type and Mesp1-deficient cardiovascular progenitor cells at early gastrulation (see the Perspective by Kelly and Sperling). When Mesp1 was eliminated, embryonic cells remained pluripotent and could not differentiate into cardiovascular progenitors. During gastrulation, the different Mesp1 progenitors rapidly became committed to a particular cell fate and heart region. Notch1 expression marked the earliest step of cardiovascular lineage segregation.

Science, this issue p. 1177; see also p. 1098

Abstract

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. We performed single-cell RNA sequencing of wild-type 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.

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