Mesp1 coordinately regulates cardiovascular fate restriction and epithelial-mesenchymal transition in differentiating ESCs.
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.
Lindsley
R Coleman
RC
Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Gill
Jennifer G
JG
Murphy
Theresa L
TL
Langer
Ellen M
EM
Cai
Mi
M
Mashayekhi
Mona
M
Wang
Wei
W
Niwa
Noriko
N
Nerbonne
Jeanne M
JM
Kyba
Michael
M
Murphy
Kenneth M
KM
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
D051792:Basic Helix-Loop-Helix Proteins; D004318:Doxycycline; D051153:Wnt Proteins; C101538:Mesp1 protein, mouse