The role of glial cells missing 2 in induced pluripotent stem cell parathyroid differentiation.

Autor: Kato T; Department of iPS Stem Cell Regenerative Medicine, Kansai Medical University, Osaka, Japan; Division of Nephrology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan. Electronic address: t-k@med.showa-u.ac.jp., Nakatsuka R; Department of iPS Stem Cell Regenerative Medicine, Kansai Medical University, Osaka, Japan; Department of Pharmacology, Faculty of Dentistry, Osaka Dental University, Osaka, Japan., Zhang R; Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Chiba, Japan., Uemura Y; Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Chiba, Japan., Yamashita H; Department of iPS Stem Cell Regenerative Medicine, Kansai Medical University, Osaka, Japan., Matsuoka Y; Department of iPS Stem Cell Regenerative Medicine, Kansai Medical University, Osaka, Japan., Shirouzu Y; Department of iPS Stem Cell Regenerative Medicine, Kansai Medical University, Osaka, Japan., Fujioka T; Department of iPS Stem Cell Regenerative Medicine, Kansai Medical University, Osaka, Japan., Hattori F; Department of iPS Stem Cell Regenerative Medicine, Kansai Medical University, Osaka, Japan., Ogata H; Department of Internal Medicine, Showa University Northern Yokohama Hospital, Kanagawa, Japan., Sakashita A; Department of Internal Medicine, Showa University Northern Yokohama Hospital, Kanagawa, Japan., Honda H; Division of Nephrology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan., Hitomi H; Department of iPS Stem Cell Regenerative Medicine, Kansai Medical University, Osaka, Japan.
Jazyk: angličtina
Zdroj: Tissue & cell [Tissue Cell] 2025 Feb; Vol. 92, pp. 102634. Date of Electronic Publication: 2024 Nov 22.
DOI: 10.1016/j.tice.2024.102634
Abstrakt: Glial cells missing 2 (GCM2) has been identified as an essential factor for parathyroid differentiation, and GCM2 silencing in parathyroid cells decreases calcium-sensing receptor (CaSR) expression. However, the role of GCM2 in parathyroid differentiation from induced pluripotent stem cells (iPSCs) is unclear. Here, we investigated the role of GCM2 in parathyroid differentiation from iPSCs using the Tet-On 3 G system. We confirmed that iPS cells transfected with GCM2/TRE3G and pCMV-Tet3G vectors express GCM2 in a doxycycline-dependent manner. Though parathyroid glands derive from the endoderm and differentiate via the third pharyngeal arch (PPE), overexpression of GCM2 in iPSCs significantly abolished the suppression of OCT4 and SOX2, suggesting inhibition of endodermal differentiation. GCM2 overexpression at the stage of differentiation into the third PPE also increased the expression levels of CaSR and parathyroid hormone, and increased the number of CaSR + /EpCAM + cells. These results suggest that GCM2 regulates parathyroid differentiation after endoderm differentiation rather than at an earlier stage.
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Databáze: MEDLINE