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Open Access Green as soon as Postprint is submitted to ZB.
Induction of MesP1 by Brachyury(T) generates the common multipotent cardiovascular stem cell.
Cardiovasc. Res. 92, 115-122 (2011)
AIMS: Our recent work demonstrated that common cardiovascular progenitor cells are characterized and induced by the expression of the transcription factor mesoderm posterior1 (MesP1) in vertebrate embryos and murine embryonic stem cells. As the proliferative potential of stem cell-derived cardiomyocytes is limited, it is crucial to understand how MesP1 expression is mediated in order to achieve reasonable and reliable yields for novel stem cell-based therapeutic options. As potential upstream regulators of MesP1, we therefore analysed Eomes and Brachyury(T), which had been controversially discussed as being crucial for cardiovasculogenic lineage formation. METHODS AND RESULTS: Wild-type and transgenic murine embryonic stem cell lines, mRNA analyses, embryoid body formation, and cell sorting revealed that the MesP1 positive population emerges from the Brachyury(T) positive fraction. In situ hybridizations using wild-type mouse embryos confirmed that Brachyury(T) colocalises with MesP1 in vivo. Likewise, shRNA-based loss of Brachyury(T) causes a dramatic decrease in MesP1 expression accompanied by reduced cardiac markers in differentiating embryonic stem cells, which is reflected in vivo via in situ hybridizations using Brachyury(T) knock-out embryos where MesP1 mRNA is greatly abolished. We finally defined a 3.4 kb proximal MesP1-promoter fragment which is directly bound and activated by Brachyury(T) via a T responsive element as shown via bandshift, chromatin immuneprecipitation, and reporter assays. CONCLUSION: Our work contributes to the understanding of the earliest cardiovasculogenic events and may become an important prerequisite for cell therapy, tissue engineering, and pharmacological testing in the culture dish using pluripotent stem cell-derived as well as directly reprogrammed cardiovascular cell types.
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Times Cited
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6.051
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38
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
MesP1; Brachyury(T); Pluripotent stem cells; Embryogenesis; Cardiovasculogenesis
Language
english
Publication Year
2011
HGF-reported in Year
2011
ISSN (print) / ISBN
0008-6363
e-ISSN
1755-3245
Journal
Cardiovascular Research
Quellenangaben
Volume: 92,
Issue: 1,
Pages: 115-122
Publisher
Oxford University Press
Reviewing status
Peer reviewed
Institute(s)
Institute of Diabetes and Regeneration Research (IDR)
Institute of Stem Cell Research (ISF)
Institute of Stem Cell Research (ISF)
POF-Topic(s)
90000 - German Center for Diabetes Research
30201 - Metabolic Health
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
30201 - Metabolic Health
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s)
Helmholtz Diabetes Center
Stem Cell and Neuroscience
Stem Cell and Neuroscience
PSP Element(s)
G-501900-231
G-502300-001
G-500890-001
G-502300-001
G-500890-001
PubMed ID
21632880
Scopus ID
80052880254
Erfassungsdatum
2011-09-09