2. Academic Validation
  3. Conversion of human fibroblasts into functional cardiomyocytes by small molecules

Conversion of human fibroblasts into functional cardiomyocytes by small molecules

  • Science. 2016 Jun 3;352(6290):1216-20. doi: 10.1126/science.aaf1502.
Nan Cao 1,  Yu Huang 2,  Jiashun Zheng 3,  C Ian Spencer 2,  Yu Zhang 1,  Ji-Dong Fu 4,  Baoming Nie 1,  Min Xie 1,  Mingliang Zhang 1,  Haixia Wang 1,  Tianhua Ma 1,  Tao Xu 1,  Guilai Shi 1,  Deepak Srivastava 5,  Sheng Ding 1
Affiliations

Affiliations

  • 1 Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA. Department of Pharmaceutical Chemistry, University of California-San Francisco, San Francisco, CA 94158, USA.
  • 2 Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA.
  • 3 Department of Biochemistry and Biophysics, University of California-San Francisco, San Francisco, CA 94158, USA. California Institute for Quantitative Biosciences, University of California-San Francisco, San Francisco, CA 94158, USA.
  • 4 Department of Medicine, Heart and Vascular Research Center, Case Western Reserve University, Cleveland, OH 44106, USA.
  • 5 Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA. Department of Pediatrics, University of California-San Francisco, San Francisco, CA 94158, USA. Department of Biochemistry and Biophysics, University of California-San Francisco, San Francisco, CA 94158, USA.
PMID: 27127239 DOI: 10.1126/science.aaf1502
Abstract

Reprogramming somatic fibroblasts into alternative lineages would provide a promising source of cells for regenerative therapy. However, transdifferentiating human cells into specific homogeneous, functional cell types is challenging. Here we show that cardiomyocyte-like cells can be generated by treating human fibroblasts with a combination of nine compounds that we term 9C. The chemically induced cardiomyocyte-like cells uniformly contracted and resembled human cardiomyocytes in their transcriptome, epigenetic, and electrophysiological properties. 9C treatment of human fibroblasts resulted in a more open-chromatin conformation at key heart developmental genes, enabling their promoters and enhancers to bind effectors of major cardiogenic signals. When transplanted into infarcted mouse hearts, 9C-treated fibroblasts were efficiently converted to chemically induced cardiomyocyte-like cells. This pharmacological approach to lineage-specific reprogramming may have many important therapeutic implications after further optimization to generate mature cardiac cells.

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