TY - JOUR
T1 - Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors
AU - Ieda, Masaki
AU - Fu, Ji Dong
AU - Delgado-Olguin, Paul
AU - Vedantham, Vasanth
AU - Hayashi, Yohei
AU - Bruneau, Benoit G.
AU - Srivastava, Deepak
N1 - Funding Information:
We are grateful to members of the Srivastava lab, to K. Tomoda for critical discussions and comments on the manuscript, to J. Olgin and C. Ding for electrophysiology assistance, to Z. Yang and K. Worringer for help with lentivirus experiments, to Y. Huang for cell transplantation experiments, to B. Taylor, G. Howard, and S. Ordway for editorial assistance and manuscript preparation, to C. Barker and L. Ta in the Gladstone Genomics core, to C. Miller and J. Fish in the Gladstone Histology core, to A. Holloway in the Gladstone Bioinformatics core, and to S. Elmes in the Laboratory for Cell Analysis in UCSF. We also thank S. Yamanaka for helpful discussions and providing pMXs-DsRed Express plasmid, T. Kitamura for Plat-E cells, J. Robbins for α-MHC promoter plasmid, T.M. Jessell for Isl1-Cre mice, and F. Costantini for R26R-EYFP mice. M.I. and Y.H. are supported by a grant from the Uehara Memorial Foundation. V.V. is supported by grants from the GlaxoSmithKline Cardiovascular Research and Education Foundation and the NIH/NHLBI. P.D.-O. was a postdoctoral scholar of the California Institute for Regenerative Medicine. D.S. and B.G.B are supported by grants from NHLBI/NIH and the California Institute for Regenerative Medicine. The J. David Gladstone Institutes received support from a National Center for Research Resources Grant RR18928-01. D.S. is a member of the Scientific Advisory Board of iPierian, Inc., and RegeneRx. B.G.B. is a member of the Scientific Advisory Board of iPierian Inc.
PY - 2010/8
Y1 - 2010/8
N2 - The reprogramming of fibroblasts to induced pluripotent stem cells (iPSCs) raises the possibility that a somatic cell could be reprogrammed to an alternative differentiated fate without first becoming a stem/progenitor cell. A large pool of fibroblasts exists in the postnatal heart, yet no single " master regulator" of direct cardiac reprogramming has been identified. Here, we report that a combination of three developmental transcription factors (i.e., Gata4, Mef2c, and Tbx5) rapidly and efficiently reprogrammed postnatal cardiac or dermal fibroblasts directly into differentiated cardiomyocyte-like cells. Induced cardiomyocytes expressed cardiac-specific markers, had a global gene expression profile similar to cardiomyocytes, and contracted spontaneously. Fibroblasts transplanted into mouse hearts one day after transduction of the three factors also differentiated into cardiomyocyte-like cells. We believe these findings demonstrate that functional cardiomyocytes can be directly reprogrammed from differentiated somatic cells by defined factors. Reprogramming of endogenous or explanted fibroblasts might provide a source of cardiomyocytes for regenerative approaches. PaperClip:
AB - The reprogramming of fibroblasts to induced pluripotent stem cells (iPSCs) raises the possibility that a somatic cell could be reprogrammed to an alternative differentiated fate without first becoming a stem/progenitor cell. A large pool of fibroblasts exists in the postnatal heart, yet no single " master regulator" of direct cardiac reprogramming has been identified. Here, we report that a combination of three developmental transcription factors (i.e., Gata4, Mef2c, and Tbx5) rapidly and efficiently reprogrammed postnatal cardiac or dermal fibroblasts directly into differentiated cardiomyocyte-like cells. Induced cardiomyocytes expressed cardiac-specific markers, had a global gene expression profile similar to cardiomyocytes, and contracted spontaneously. Fibroblasts transplanted into mouse hearts one day after transduction of the three factors also differentiated into cardiomyocyte-like cells. We believe these findings demonstrate that functional cardiomyocytes can be directly reprogrammed from differentiated somatic cells by defined factors. Reprogramming of endogenous or explanted fibroblasts might provide a source of cardiomyocytes for regenerative approaches. PaperClip:
KW - DEVBIO
KW - HUMDISEASE
KW - STEMCELL
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U2 - 10.1016/j.cell.2010.07.002
DO - 10.1016/j.cell.2010.07.002
M3 - Article
C2 - 20691899
AN - SCOPUS:77955321344
SN - 0092-8674
VL - 142
SP - 375
EP - 386
JO - Cell
JF - Cell
IS - 3
ER -