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Science. 2018 Mar 9;359(6380):1177-1181. doi: 10.1126/science.aao4174. Epub 2018 Jan 25.

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

Author information

1
Université Libre de Bruxelles, Laboratory of Stem Cells and Cancer, Brussels B-1070, Belgium.
2
Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK.
3
Wellcome and Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
4
Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK. bg200@cam.ac.uk cedric.blanplain@ulb.ac.be.
5
Université Libre de Bruxelles, Laboratory of Stem Cells and Cancer, Brussels B-1070, Belgium. bg200@cam.ac.uk cedric.blanplain@ulb.ac.be.
6
WELBIO, Université Libre de Bruxelles, Brussels B-1070, Belgium.

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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PMID:
29371425
PMCID:
PMC6556615
DOI:
10.1126/science.aao4174
[Indexed for MEDLINE]
Free PMC Article

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