2. Academic Validation
  3. Signaling pathway-based culture condition improves differentiation potential of canine induced pluripotent stem cells

Signaling pathway-based culture condition improves differentiation potential of canine induced pluripotent stem cells

  • Stem Cell Reports. 2025 Oct 14;20(10):102640. doi: 10.1016/j.stemcr.2025.102640.
Toshiya Nishimura 1,  Kazuto Kimura 2,  Kyomi J Igarashi 3,  Kohei Shishida 4,  Hiroko Sugisaki 4,  Masaya Tsukamoto 4,  Aadhavan Balakumar 5,  Chihiro Funamoto 6,  Masumi Hirabayashi 7,  Amir Kol 5,  Shingo Hatoya 8
Affiliations

Affiliations

  • 1 Premium Research Institute for Human Metaverse Medicine (WPI-PRIMe), The University of Osaka, Suita, Osaka 565-0871, Japan. Electronic address: tnishimu.kbb@osaka-u.ac.jp.
  • 2 Department of Advanced Pathobiology, Graduate School of Veterinary Sciences, Osaka Metropolitan University, Izumisano, Osaka 598-8531, Japan; Department of Pathology, Microbiology & Immunology, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA.
  • 3 Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
  • 4 Department of Advanced Pathobiology, Graduate School of Veterinary Sciences, Osaka Metropolitan University, Izumisano, Osaka 598-8531, Japan.
  • 5 Department of Pathology, Microbiology & Immunology, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA.
  • 6 Division of Stem Cell and Organoid Medicine, Department of Genome Biology, Graduate School of Medicine, The University of Osaka, Osaka 565-0871, Japan.
  • 7 Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki, Aichi 444-8787, Japan; The Graduate University of Advanced Studies, Okazaki, Aichi 444-8787, Japan.
  • 8 Department of Advanced Pathobiology, Graduate School of Veterinary Sciences, Osaka Metropolitan University, Izumisano, Osaka 598-8531, Japan. Electronic address: hatoya@omu.ac.jp.
PMID: 40972586 DOI: 10.1016/j.stemcr.2025.102640
Abstract

Naturally occurring diseases in companion dogs are increasingly being recognized as valuable translational disease models. While induced pluripotent stem cell (iPSC) technology had revolutionized the field of human bio-medical research, canine iPSC (ciPSC) technology is still in its infancy, and robust canine-specific iPSC medium formulations and differentiation protocols are lacking. Here, we have established NANOG-reporter ciPSC lines and found that Fibroblast Growth Factor (FGF), activin/transforming growth factor (TGF)-β, and Wnt signals were critical for the robust maintenance of ciPSCs. Manipulating these signaling pathways stabilized the culture of ciPSC regardless of the cell line or basal medium. ciPSCs cultured in the optimized medium showed a homogenized global gene expression pattern. Furthermore, the ciPSCs cultured in this medium successfully differentiated into cardiomyocytes displaying homogenous contraction as well as sarcomere alignment. This robust culture condition provides a valuable resource to facilitate the utilization of ciPSCs for various studies, including human disease modeling.

Keywords

animal; canine; cardiomyocyte; gene editing; induced pluripotent stem cells; primed pluripotent stem cells; reporter line.

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