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Nat Cell Biol. 2014 Sep;16(9):829-40. doi: 10.1038/ncb3024. Epub 2014 Aug 24.

Early lineage restriction in temporally distinct populations of Mesp1 progenitors during mammalian heart development.

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1] Université Libre de Bruxelles, IRIBHM, Brussels B-1070, Belgium [2].
Université Libre de Bruxelles, IRIBHM, Brussels B-1070, Belgium.
1] Cavendish Laboratory, Department of Physics, J. J. Thomson Avenue, Cambridge CB3 0HE, UK [2] The Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
Functional Genomics Core, Institute for Research in Biomedicine, Barcelona 08028, Spain.
Université Catholique de Louvain, de Duve Institute, Brussels B-1200, Belgium.
1] Université Libre de Bruxelles, IRIBHM, Brussels B-1070, Belgium [2] Department of Cardiology, Hopital Erasme, Brussels B-1070, Belgium.
1] Université Libre de Bruxelles, IRIBHM, Brussels B-1070, Belgium [2] WELBIO, Université Libre de Bruxelles, Brussels B-1070, Belgium.


Cardiac development arises from two sources of mesoderm progenitors, the first heart field (FHF) and the second (SHF). Mesp1 has been proposed to mark the most primitive multipotent cardiac progenitors common for both heart fields. Here, using clonal analysis of the earliest prospective cardiovascular progenitors in a temporally controlled manner during early gastrulation, we found that Mesp1 progenitors consist of two temporally distinct pools of progenitors restricted to either the FHF or the SHF. FHF progenitors were unipotent, whereas SHF progenitors were either unipotent or bipotent. Microarray and single-cell PCR with reverse transcription analysis of Mesp1 progenitors revealed the existence of molecularly distinct populations of Mesp1 progenitors, consistent with their lineage and regional contribution. Together, these results provide evidence that heart development arises from distinct populations of unipotent and bipotent cardiac progenitors that independently express Mesp1 at different time points during their specification, revealing that the regional segregation and lineage restriction of cardiac progenitors occur very early during gastrulation.

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