title: Mesp1 patterns mesoderm into cardiac, hematopoietic, or skeletal myogenic progenitors in a context-dependent manner.
abstract: Mesp1 is regarded as the master regulator of cardiovascular development, initiating the cardiac transcription factor cascade to direct the generation of cardiac mesoderm. To define the early embryonic cell population that responds to Mesp1, we performed pulse inductions of gene expression over tight temporal windows following embryonic stem cell differentiation. Remarkably, instead of promoting cardiac differentiation in the initial wave of mesoderm, Mesp1 binds to the Tal1 (Scl) +40 kb enhancer and generates Flk-1+ precursors expressing Etv2 (ER71) and Tal1 that undergo hematopoietic differentiation. The second wave of mesoderm responds to Mesp1 by differentiating into PDGFRα+ precursors that undergo cardiac differentiation. Furthermore, in the absence of serum-derived factors, Mesp1 promotes skeletal myogenic differentiation. Lineage tracing revealed that the majority of yolk sac and many adult hematopoietic cells derive from Mesp1+ precursors. Thus, Mesp1 is a context-dependent determination factor, integrating the stage of differentiation and the signaling environment to specify different lineage outcomes.
authors: Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA.
authors: Sunny Sun-Kin
authors: SS
authors: Chan
authors: Xiaozhong
authors: X
authors: Shi
authors: Akira
authors: A
authors: Toyama
authors: Robert W
authors: RW
authors: Arpke
authors: Abhijit
authors: A
authors: Dandapat
authors: Michelina
authors: M
authors: Iacovino
authors: Jinjoo
authors: J
authors: Kang
authors: Gengyun
authors: G
authors: Le
authors: Hannah R
authors: HR
authors: Hagen
authors: Daniel J
authors: DJ
authors: Garry
authors: Michael
authors: M
authors: Kyba
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D020029:Base Pairing / Q000235:genetics; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D019521:Body Patterning; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000235:genetics; D006321:Heart / Q000196:embryology*; D006410:Hematopoiesis; D006413:Hematopoietic System / Q000166:cytology / Q000196:embryology*; D008648:Mesoderm / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D051379:Mice; D018101:Mice, Inbred mdx; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000196:embryology* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D011485:Protein Binding; D055503:Protein Multimerization; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism / Q000473:pathology; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D015017:Yolk Sac / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; C503994:ER71 protein, mouse; C101538:Mesp1 protein, mouse; C489366:Tal1 protein, mouse
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