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PMID: 22848549 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

DMH1, a novel BMP small molecule inhibitor, increases cardiomyocyte progenitors and promotes cardiac differentiation in mouse embryonic stem cells.

PloS one ·Vol. 7 ·No. 7 ·2012-00-00 ·Pages e41627

Ao A, Hao J, Hopkins CR, Hong CC

Abstract

The possibility of using cell-based therapeutics to treat cardiac failure has generated significant interest since the initial introduction of stem cell-based technologies. However, the methods to quickly and robustly direct stem cell differentiation towards cardiac cell types have been limited by a reliance on recombinant growth factors to provide necessary biological cues. We report here the use of dorsomorphin homologue 1 (DMH1), a second-generation small molecule BMP inhibitor based on dorsomorphin, to efficiently induce beating cardiomyocyte formation in mouse embryonic stem cells (ESCs) and to specifically upregulate canonical transcriptional markers associated with cardiac development. DMH1 differs significantly from its predecessor by its ability to enrich for pro-cardiac progenitor cells that respond to late-stage Wnt inhibition using XAV939 and produce secondary beating cardiomyocytes. Our study demonstrates the utility of small molecules to complement existing in vitro cardiac differentiation protocols and highlights the role of transient BMP inhibition in cardiomyogenesis.

MeSH Terms
Animals Bone Morphogenetic Proteins/antagonists & inhibitors Cell Differentiation/drug effects Cell Line Embryonic Stem Cells/cytology,drug effects,metabolism Mice Myocytes, Cardiac/cytology Pyrazoles/chemistry,pharmacology Pyrimidines/chemistry,pharmacology Transcriptome/drug effects Wnt Proteins/antagonists & inhibitors
Chemicals
Bone Morphogenetic Proteins Pyrazoles Pyrimidines Wnt Proteins dorsomorphin
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Ao Ada
Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America. adaao05@gmail.com
Hao Jijun
Hopkins Corey R
Hong Charles C
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Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
DOI
10.1371/journal.pone.0041627
Email
adaao05@gmail.com
Published
2012-00-00
Epub
2012-00-27
Pages
e41627
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC3407188
Subset
IM
Grants
NHLBI NIH HHS · R01 HL104040 · United States
NHLBI NIH HHS · T32 HL105334 · United States
NHLBI NIH HHS · 1T32HL105334-1A1 · United States
NHLBI NIH HHS · 5R01HL104040-02 · United States
External Links
PubMed source DOI: 10.1371/journal.pone.0041627 PMC Full Text View journal details
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