Histone acetylation favours the cardiovascular commitment of adipose tissue-derived stromal cells
Autor: | Sebastiano Sciarretta, Leonardo Schirone, Elena De Falco, Isotta Chimenti, Antonella Bordin, Mohsen Ibrahim, Michele Madonna, Francesca Pagano, Eleonora Scaccia, Luca Fianchini, Silvia Palmerio, Francesco Angelini, Giacomo Frati |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Stromal cell medicine.drug_class Cell fate commitment 03 medical and health sciences Adipocytes Medicine Animals Humans Myocytes Cardiac Epigenetics Aged Histone Acetyltransferases biology business.industry Histone deacetylase inhibitor Transdifferentiation adipose stromal cells cardiac troponin I cardiac transdifferentiation cardiomyocytes histone 3 SAHA hemic and immune systems Acetylation Middle Aged Chromatin Rats Histone Deacetylase Inhibitors 030104 developmental biology Histone Adipose Tissue Animals Newborn biology.protein Cancer research Female Stromal Cells Cardiology and Cardiovascular Medicine business |
Zdroj: | International journal of cardiology. 243 |
ISSN: | 1874-1754 |
Popis: | Background Although adipose stromal cells (ASCs) retain the ability to transdifferentiate at low rate towards the cardiac lineage, the potential mechanisms underlying such process have still to be elucidated. Methods Since chromatin state modifications are involved in several processes regulating the cellular cell fate commitment, we aimed at evaluating the role of histone protein acetylation in the cardiovascular-like transdifferentiation of ASCs. Results We found a clear increase of histone 3 acetylation status paralleled by a significant upregulation of cardiac TnI gene expression, in ASCs treated with the conditioned medium of primary cardiomyocyte cell cultures for 72h. This result suggests that histone acetylation contributes to the transdifferentiation of ASCs towards the cardiac lineage. In order to directly test this hypothesis, ASCs cultured with regular medium were treated with SAHA, a pan histone deacetylase inhibitor. We found that SAHA enhanced the cardiac permissive state of ASCs, increasing both mRNA and protein expression of cardiovascular genes, particularly cTnI. This suggests that histone acetylation induction is sufficient to promote cardiovascular transdifferentiation. Conclusions The control of ASC fate by epigenetic regulators might be an interesting tool to boost both cardiac commitment and regenerative capacities of ASCs. |
Databáze: | OpenAIRE |
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