Abstracts (poster) - Wissenschaft Online

Niels Boeckel, Masamichi Koyanagi, Masayoshi Iwasaki, Andreas M. Zeiher, Stefanie
Dimmeler
Oct3/4 and Klf4 promoter status in multipotent circulating
mesangioblasts
Histone modification plays an important role in regulation of gene transcription. Active
and inactive promoters are characterized by different histone modifications.
Transcriptional repression is followed e.g. by a pronounced increase in histone H3
methylation on Lysine 9, while transcriptional active promoters are characterized by
acetylation at histone H3 lysine 9 and lysine 14. Previous studies demonstrated
pronounced increase of Histone 3 lysine 9 trimetyhlation and decrease of histone H3
acetylation of the Oct3/4 Promoter during ES cell differentiation. Recently, we identified
clonally expandable, telomerase-expressing stem cells, which can be isolated from
peripheral blood of children undergoing cardiac surgery. The marker profile of the
clonally expanded cells is distinct from endothelial progenitor cells, hematopoietic or
mesenchymal stem cells but resembles multipotent embryonic mesoangioblasts (MAB),
which are multipotent progenitors of mesodermal tissue originally isolated from the
embryonic dorsal aorta and characterised by expression of mesenchymal and endothelial
markers. Indeed, circulating MABs are multipotent and differentiate into endothelial
cells, smooth muscle cells, and cardiomyocytes in vitro and in vivo, and improve
functional recovery after hind limb ischemia and acute myocardial infarction model.
Circulating MAB show telomerase activity and express 3 out of 4 genes previously shown
to induce pluripotency namely Oct3/4, KLF4 and c-myc while Sox2 was not expressed.
Oct3/4 expression was confirmed by RT-PCR and immunostaining. We also performed
chromatin immunoprecipitation to analyze the histone modification status of Oct3/4 and
KLF4 promoters in MAB. We found that histone H3 lysine 9 and 14 were acetylated,
whereas H3 lysine 9 was not trimethylated on both promoters. Taken together, these
findings demonstrate the active status of Oct3/4 and KLF4 promoter in circulating MAB,
which was associated with expression of both genes. Demonstrating active status of
stem cell markers support the evidence of multipotency of adult stem cell.
contact:
Niels Boeckel
University of Frankfurt
Dept. of Internal Medicine III Molecular Cardiology
NielsBoeckel@gmx.de
Theodor-Stern-Kai 7
60590 Frankfurt (Germany)