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

• Published in: Nature cell biology Vol. 16; no. 9; pp. 829 - 840
• Main Authors: Lescroart, Fabienne, Chabab, Samira, Lin, Xionghui, Rulands, Steffen, Paulissen, Catherine, Rodolosse, Annie, Auer, Herbert, Achouri, Younes, Dubois, Christine, Bondue, Antoine, Simons, Benjamin D., Blanpain, Cédric
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2014; Nature Publishing Group
• Subjects: 13/31; 14; 14/19; 14/35; 38/15; 38/61; 49/39; 631/136/2086; 631/136/532/2118; 631/136/532/2118/2440; 64/110; Analysis; Animals; Basic Helix-Loop-Helix Transcription Factors - genetics; Basic Helix-Loop-Helix Transcription Factors - metabolism; Body Patterning; Cancer Research; Cell Biology; Cell Differentiation; Cell Lineage; Cellular Biology; Development Biology; Developmental Biology; Embryology and Organogenesis; Endothelial growth factors; Female; Fetal Heart - cytology; Fetal Heart - metabolism; Gene Expression Regulation, Developmental; Genetic aspects; Heart; Heart Atria - cytology; Heart Atria - embryology; Heart Atria - metabolism; Heart Ventricles - cytology; Heart Ventricles - embryology; Heart Ventricles - metabolism; Life Sciences; Mammals; Mathematics; Medical research; Mice; Mice, Transgenic; Organ Specificity; Physiological aspects; Probability; Stem Cells; Stem Cells - physiology; Transcriptome; Transgenic animals; Belgium; United Kingdom > UK
• ISSN: 1465-7392; 1476-4679; 1476-4679
• DOI: 10.1038/ncb3024

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. The heart arises from distinct progenitors. Blanpain and colleagues use clonal analysis to demonstrate that early prospective cardiac progenitors, marked by Mesp1 appearing at gastrulation, are already restricted to a particular lineage and heart region.