Journal
CELL REPORTS
Volume 6, Issue 5, Pages 951-960Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2014.01.038
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Funding
- California Institute for Regenerative Medicine
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
- National Heart, Lung, and Blood Institute
- National Eye Institute/National Institutes of Health
- Roddenberry Foundation
- William K. Bowes, Jr. Foundation
- Gladstone Institutes
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It was recently shown that mouse fibroblasts could be reprogrammed into cells of a cardiac fate by forced expression of multiple transcription factors and microRNAs. For ultimate application of such a reprogramming strategy for cell-based therapy or in vivo cardiac regeneration, reducing or eliminating the genetic manipulations by small molecules would be highly desirable. Here, we report the identification of a defined small-molecule cocktail that enables the highly efficient conversion of mouse fibroblasts into cardiac cells with only one transcription factor, Oct4, without any evidence of entrance into the pluripotent state. Small-molecule-induced cardiomyocytes spontaneously contract and exhibit a ventricular phenotype. Furthermore, these induced cardiomyocytes pass through a cardiac progenitor stage. This study lays the foundation for future pharmacological reprogramming approaches and provides a small-molecule condition for investigation of the mechanisms underlying the cardiac reprogramming process.
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