PuSH - Publikationsserver des Helmholtz Zentrums München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
David, R.* ; Jarsch, V.B.* ; Schwarz, F.* ; Nathan, P.* ; Gegg, M. ; Lickert, H. ; Franz, W.M.*

Induction of MesP1 by Brachyury(T) generates the common multipotent cardiovascular stem cell.

Cardiovasc. Res. 92, 115-122 (2011)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
6.051
1.663
38
58
Tags
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern

Zusatzinfos bearbeiten
Eigene Tags bearbeiten
Privat
Eigene Anmerkung bearbeiten
Privat
Auf Publikationslisten für
Homepage nicht anzeigen
Als besondere Publikation
markieren
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter MesP1; Brachyury(T); Pluripotent stem cells; Embryogenesis; Cardiovasculogenesis
Sprache englisch
Veröffentlichungsjahr 2011
HGF-Berichtsjahr 2011
ISSN (print) / ISBN 0008-6363
e-ISSN 1755-3245
Zeitschrift Cardiovascular Research
Quellenangaben Band: 92, Heft: 1, Seiten: 115-122 Artikelnummer: , Supplement: ,
Verlag Oxford University Press
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Regeneration Research (IDR)
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
Forschungsfeld(er) Helmholtz Diabetes Center
Stem Cell and Neuroscience
PSP-Element(e) G-501900-231
G-502300-001
G-500890-001
PubMed ID 21632880
DOI 10.1093/cvr/cvr158
Scopus ID 80052880254
Erfassungsdatum 2011-09-09
[➜Korrektur melden]