Direct cardiac reprogramming by defined factors

DOI 参考文献37件
  • Ieda Masaki
    Department of Clinical and Molecular Cardiovascular Research, Keio University School of Medicine, Tokyo, Japan Department of Cardiology, Keio University School of Medicine, Tokyo, Japan JST, CREST, Tokyo, Japan

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The potency of specific transcription factors as cell fate determinants was first demonstrated by the discovery of MyoD, a master gene for skeletal muscle differentiation, and by the subsequent identification of several genes as lineage-converting factors within the blood cell lineage. These pioneer works led to the landmark study by Dr. Yamanaka and colleagues that is reprogramming of somatic cells into a pluripotent state by transduction of the four stem cell-specific transcription factors, Oct4, Sox2, Klf4, and c-Myc. This study fundamentally altered the approach to regenerative medicine and also inspired a new strategy to generate desired cell types by introducing combinations of lineage-specific transcription factors. In fact, it has been demonstrated that a diverse range of cell types, such as pancreatic β-cells, neurons, chondrocytes, and hepatocytes, can be induced from differentiated somatic cells using lineage specific-reprogramming factors. We and other reported that functional cardiomyocytes can be generated directly from fibroblasts using several combinations of cardiac-enriched factors in vitro and in vivo. The present article reviews the pioneering and recent studies in cellular reprogramming, and discusses the perspectives and challenges of direct cardiac reprogramming in regenerative therapy.

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