title: Sall1 transiently marks undifferentiated heart precursors and regulates their fate.
abstract: Cardiac progenitor cells (CPCs) are a crucial source of cells in cardiac development and regeneration. However, reported CPCs are heterogeneous, and no gene has been identified to transiently mark undifferentiated CPCs throughout heart development. Here we show that Spalt-like gene 1 (Sall1), a zing-finger transcription factor, is expressed in undifferentiated CPCs giving rise to both left and right ventricles. Sall1 was transiently expressed in precardiac mesoderm contributing to the first heart field (left ventricle precursors) but not in the field itself. Similarly, Sall1 expression was maintained in the second heart field (outflow tract/right ventricle precursors) but not in cardiac cells. In vitro, high levels of Sall1 at mesodermal stages enhanced cardiomyogenesis, whereas its continued expression suppressed cardiac differentiation. Our study demonstrates that Sall1 marks CPCs in an undifferentiated state and regulates cardiac differentiation. These findings provide fundamental insights into CPC maintenance, which can be instrumental for CPC-based regenerative medicine.
authors.affiliation: Division of Cardiovascular Regeneration, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo, Tokyo 113-0032, Japan; Department of Biological Sciences, Graduate School of Science, University of Tokyo, 7-3-1, Hongo, Bunkyo, Tokyo 113-0033, Japan.
authors.forename: Yuika
authors.initials: Y
authors.lastname: Morita
authors.affiliation: Division of Cardiology, Institute for Cell Engineering, Johns Hopkins University School of Medicine, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Andersen
authors.affiliation: Department of Reprogramming Science, Centre for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan; AMED, Research Center Network for Realization of Regenerative Medicine, Projects for Technological Development, Japan; JST PESTO, Understanding Life by iPS Cells Technology, Sanbancho building, Sanbancho 5, Chiyoda-ku, Tokyo 102-0075, Japan.
authors.forename: Akitsu
authors.initials: A
authors.lastname: Hotta
authors.affiliation: Division of Cardiovascular Regeneration, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo, Tokyo 113-0032, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tsukahara
authors.affiliation: Department of Reprogramming Science, Centre for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Sasagawa
authors.affiliation: Division of Cardiovascular Regeneration, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo, Tokyo 113-0032, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Hayashida
authors.affiliation: Division of Cardiovascular Regeneration, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo, Tokyo 113-0032, Japan.
authors.forename: Chizuko
authors.initials: C
authors.lastname: Koga
authors.affiliation: Department of Reprogramming Science, Centre for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Misato
authors.initials: M
authors.lastname: Nishikawa
authors.affiliation: Mammalian Development Laboratory, National Institute of Genetics, 1111 Yata, Mishima, Shizuoka 411-8540, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Saga
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Medicine, School of Medicine, University of California, San Diego, USA.
authors.forename: Sylvia M
authors.initials: SM
authors.lastname: Evans
authors.affiliation: Division of Cardiovascular Regeneration, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo, Tokyo 113-0032, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Koshiba-Takeuchi
authors.affiliation: Department of Kidney Development, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto, 860-0811, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Nishinakamura
authors.affiliation: Department of Reprogramming Science, Centre for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan; AMED, Research Center Network for Realization of Regenerative Medicine, Projects for Technological Development, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Division of Cardiology, Institute for Cell Engineering, Johns Hopkins University School of Medicine, USA.
authors.forename: Chulan
authors.initials: C
authors.lastname: Kwon
authors.affiliation: Division of Cardiovascular Regeneration, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo, Tokyo 113-0032, Japan; Department of Biological Sciences, Graduate School of Science, University of Tokyo, 7-3-1, Hongo, Bunkyo, Tokyo 113-0033, Japan; AMED, Research Center Network for Realization of Regenerative Medicine, Projects for Technological Development, Japan; JST PESTO, Understanding Life by iPS Cells Technology, Sanbancho building, Sanbancho 5, Chiyoda-ku, Tokyo 102-0075, Japan. Electronic address: junjunjunta@gmail.com.
authors.forename: Jun K
authors.initials: JK
authors.lastname: Takeuchi
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D006352:Heart Ventricles / Q000254:growth & development* / Q000378:metabolism; D006801:Humans; D051379:Mice; D009206:Myocardium / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism
chemical_list: C491254:Sall1 protein, mouse; D014157:Transcription Factors
keywords: Cardiac development; Cardiac progenitor; Cardiac transcription factors; ES/iPS cells