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J Mol Cell Cardiol. 2016 Mar;92:158-62. doi: 10.1016/j.yjmcc.2016.02.008. Epub 2016 Feb 11.

Sall1 transiently marks undifferentiated heart precursors and regulates their fate.

Author information

1
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.
2
Division of Cardiology, Institute for Cell Engineering, Johns Hopkins University School of Medicine, USA.
3
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.
4
Division of Cardiovascular Regeneration, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo, Tokyo 113-0032, Japan.
5
Department of Reprogramming Science, Centre for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
6
Mammalian Development Laboratory, National Institute of Genetics, 1111 Yata, Mishima, Shizuoka 411-8540, Japan.
7
Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Medicine, School of Medicine, University of California, San Diego, USA.
8
Department of Kidney Development, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto, 860-0811, Japan.
9
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.
10
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.

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.

KEYWORDS:

Cardiac development; Cardiac progenitor; Cardiac transcription factors; ES/iPS cells

PMID:
26876450
PMCID:
PMC4789172
DOI:
10.1016/j.yjmcc.2016.02.008
[Indexed for MEDLINE]
Free PMC Article

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