title: Small molecules enable cardiac reprogramming of mouse fibroblasts with a single factor, Oct4.
abstract: 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.
authors.affiliation: Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA; Roddenberry Center for Stem Cell Biology and Medicine at Gladstone, San Francisco, CA 94158, USA.
authors.forename: Haixia
authors.initials: H
authors.lastname: Wang
authors.affiliation: Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA; Roddenberry Center for Stem Cell Biology and Medicine at Gladstone, San Francisco, CA 94158, USA.
authors.forename: Nan
authors.initials: N
authors.lastname: Cao
authors.affiliation: Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA; Roddenberry Center for Stem Cell Biology and Medicine at Gladstone, San Francisco, CA 94158, USA.
authors.forename: C Ian
authors.initials: CI
authors.lastname: Spencer
authors.affiliation: Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA; Roddenberry Center for Stem Cell Biology and Medicine at Gladstone, San Francisco, CA 94158, USA.
authors.forename: Baoming
authors.initials: B
authors.lastname: Nie
authors.affiliation: Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA; Roddenberry Center for Stem Cell Biology and Medicine at Gladstone, San Francisco, CA 94158, USA.
authors.forename: Tianhua
authors.initials: T
authors.lastname: Ma
authors.affiliation: Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA; Roddenberry Center for Stem Cell Biology and Medicine at Gladstone, San Francisco, CA 94158, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.affiliation: Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA; Roddenberry Center for Stem Cell Biology and Medicine at Gladstone, San Francisco, CA 94158, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA; Roddenberry Center for Stem Cell Biology and Medicine at Gladstone, San Francisco, CA 94158, USA.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA; Roddenberry Center for Stem Cell Biology and Medicine at Gladstone, 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.
authors.forename: Deepak
authors.initials: D
authors.lastname: Srivastava
authors.affiliation: Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA; Roddenberry Center for Stem Cell Biology and Medicine at Gladstone, San Francisco, CA 94158, USA; Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94158, USA. Electronic address: sheng.ding@gladstone.ucsf.edu.
authors.forename: Sheng
authors.initials: S
authors.lastname: Ding
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D065150:Cellular Reprogramming / Q000187:drug effects* / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D054852:Small Molecule Libraries / Q000494:pharmacology*
chemical_list: D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D054852:Small Molecule Libraries