title: Mesp1 coordinately regulates cardiovascular fate restriction and epithelial-mesenchymal transition in differentiating ESCs.
abstract: Wnt signaling is required for development of mesoderm-derived lineages and expression of transcription factors associated with the primitive streak. In a functional screen, we examined the mesoderm-inducing capacity of transcription factors whose expression was Wnt-dependent in differentiating ESCs. In contrast to many inactive factors, we found that mesoderm posterior 1 (Mesp1) promoted mesoderm development independently of Wnt signaling. Transient Mesp1 expression in ESCs promotes changes associated with epithelial-mesenchymal transition (EMT) and induction of Snai1, consistent with a role in gastrulation. Mesp1 expression also restricted the potential fates derived from ESCs, generating mesoderm progenitors with cardiovascular, but not hematopoietic, potential. Thus, in addition to its effects on EMT, Mesp1 may be capable of generating the recently identified multipotent cardiovascular progenitor from ESCs in vitro.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
authors.forename: R Coleman
authors.initials: RC
authors.lastname: Lindsley
authors.forename: Jennifer G
authors.initials: JG
authors.lastname: Gill
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Murphy
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Langer
authors.forename: Mi
authors.initials: M
authors.lastname: Cai
authors.forename: Mona
authors.initials: M
authors.lastname: Mashayekhi
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Noriko
authors.initials: N
authors.lastname: Niwa
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Nerbonne
authors.forename: Michael
authors.initials: M
authors.lastname: Kyba
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Murphy
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D002319:Cardiovascular System / Q000166:cytology*; D002454:Cell Differentiation / Q000187:drug effects; D004318:Doxycycline / Q000494:pharmacology; D053595:Embryonic Stem Cells / Q000166:cytology*; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D051153:Wnt Proteins / Q000502:physiology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004318:Doxycycline; D051153:Wnt Proteins; C101538:Mesp1 protein, mouse