Integration of Bmp and Wnt signaling by Hopx specifies commitment of cardiomyoblasts

In the heart, multiple cell types work together. Cardiac progenitor cells give rise to cardiomyocyte, endothelial, or smooth muscle lineages. However, the identity of a marker specific to cardiomyocyte formation has been elusive. Jain et al. now identify a specialized progenitor population that is c...

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Published in:Science (American Association for the Advancement of Science) 2015-06, Vol.348 (6242), p.1444-1444
Main Authors: Jain, Rajan, Li, Deqiang, Gupta, Mudit, Manderfield, Lauren J., Ifkovits, Jamie L., Wang, Qiaohong, Liu, Feiyan, Liu, Ying, Poleshko, Andrey, Padmanabhan, Arun, Raum, Jeffrey C., Li, Li, Morrisey, Edward E., Lu, Min Min, Won, Kyoung-Jae, Epstein, Jonathan A.
Format: Article
Language:English
Subjects:
Cells (biology)
Genes
Heart
Individualized Instruction
Markers
Muscles
Regenerative
Repressing
RESEARCH ARTICLE SUMMARY
Stem cells
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Summary:In the heart, multiple cell types work together. Cardiac progenitor cells give rise to cardiomyocyte, endothelial, or smooth muscle lineages. However, the identity of a marker specific to cardiomyocyte formation has been elusive. Jain et al. now identify a specialized progenitor population that is committed exclusively to forming cardiomyocytes. They also identify the niche signals that promote lineage commitment and the mechanisms involved in making cardiomyocytes. The findings may help in the development of future cell-based regenerative therapeutics for heart disease. Science , this issue 10.1126/science.aaa6071 Identification of the committed cardiomyoblast that retains proliferative potential may inform cardiac regenerative therapeutics. Cardiac progenitor cells are multipotent and give rise to cardiac endothelium, smooth muscle, and cardiomyocytes. Here, we define and characterize the cardiomyoblast intermediate that is committed to the cardiomyocyte fate, and we characterize the niche signals that regulate commitment. Cardiomyoblasts express Hopx, which functions to coordinate local Bmp signals to inhibit the Wnt pathway, thus promoting cardiomyogenesis. Hopx integrates Bmp and Wnt signaling by physically interacting with activated Smads and repressing Wnt genes. The identification of the committed cardiomyoblast that retains proliferative potential will inform cardiac regenerative therapeutics. In addition, Bmp signals characterize adult stem cell niches in other tissues where Hopx-mediated inhibition of Wnt is likely to contribute to stem cell quiescence and to explain the role of Hopx as a tumor suppressor.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.aaa6071