Mesp1 acts as a master regulator of multipotent cardiovascular progenitor specification.
During embryonic development, multipotent cardiovascular progenitor cells are specified from early mesoderm. Using mouse ESCs in which gene expression can be temporally regulated, we have found that transient expression of Mesp1 dramatically accelerates and enhances multipotent cardiovascular progenitor specification through an intrinsic and cell autonomous mechanism. Genome-wide transcriptional analysis indicates that Mesp1 rapidly activates and represses a discrete set of genes, and chromatin immunoprecipitation shows that Mesp1 directly binds to regulatory DNA sequences located in the promoter of many key genes in the core cardiac transcriptional machinery, resulting in their rapid upregulation. Mesp1 also directly represses the expression of key genes regulating other early mesoderm and endoderm cell fates. Our results demonstrate that Mesp1 acts as a key regulatory switch during cardiovascular specification, residing at the top of the hierarchy of the gene network responsible for cardiovascular cell-fate determination.
Bondue
Antoine
A
Université Libre de Bruxelles, IRIBHM, B-1070 Brussels, Belgium.
Lapouge
Gaëlle
G
Paulissen
Catherine
C
Semeraro
Claudio
C
Iacovino
Michelina
M
Kyba
Michael
M
Blanpain
Cédric
C
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000502:physiology*; D002319:Cardiovascular System / Q000166:cytology*; D002454:Cell Differentiation / Q000502:physiology*; D047108:Embryonic Development; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology / Q000502:physiology; D018257:Helix-Loop-Helix Motifs / Q000502:physiology; D006706:Homeostasis; D051379:Mice; D009206:Myocardium / Q000166:cytology; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000502:physiology
D051792:Basic Helix-Loop-Helix Proteins; C101538:Mesp1 protein, mouse