In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes

Li Qian, Yu Huang, C. Ian Spencer, Amy Foley, Vasanth Vedantham, Lei Liu, Simon J. Conway, Ji-dong Fu and Deepak Srivastava ()
Additional contact information
Li Qian: Gladstone Institute of Cardiovascular Disease
Yu Huang: Gladstone Institute of Cardiovascular Disease
C. Ian Spencer: Gladstone Institute of Cardiovascular Disease
Amy Foley: Gladstone Institute of Cardiovascular Disease
Vasanth Vedantham: Gladstone Institute of Cardiovascular Disease
Lei Liu: Gladstone Institute of Cardiovascular Disease
Simon J. Conway: Developmental Biology and Neonatal Medicine Research Program, Indiana University School of Medicine
Ji-dong Fu: Gladstone Institute of Cardiovascular Disease
Deepak Srivastava: Gladstone Institute of Cardiovascular Disease

Nature, 2012, vol. 485, issue 7400, 593-598

Abstract: Abstract The reprogramming of adult cells into pluripotent cells or directly into alternative adult cell types holds great promise for regenerative medicine. We reported previously that cardiac fibroblasts, which represent 50% of the cells in the mammalian heart, can be directly reprogrammed to adult cardiomyocyte-like cells in vitro by the addition of Gata4, Mef2c and Tbx5 (GMT). Here we use genetic lineage tracing to show that resident non-myocytes in the murine heart can be reprogrammed into cardiomyocyte-like cells in vivo by local delivery of GMT after coronary ligation. Induced cardiomyocytes became binucleate, assembled sarcomeres and had cardiomyocyte-like gene expression. Analysis of single cells revealed ventricular cardiomyocyte-like action potentials, beating upon electrical stimulation, and evidence of electrical coupling. In vivo delivery of GMT decreased infarct size and modestly attenuated cardiac dysfunction up to 3 months after coronary ligation. Delivery of the pro-angiogenic and fibroblast-activating peptide, thymosin β4, along with GMT, resulted in further improvements in scar area and cardiac function. These findings demonstrate that cardiac fibroblasts can be reprogrammed into cardiomyocyte-like cells in their native environment for potential regenerative purposes.

Date: 2012
References: Add references at CitEc
Citations: View citations in EconPapers (6)

Downloads: (external link)
https://www.nature.com/articles/nature11044 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:485:y:2012:i:7400:d:10.1038_nature11044

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature11044

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().