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

被引:0
作者
Kato, Tadashi [1 ,2 ]
Nakatsuka, Ryusuke [1 ,3 ]
Zhang, Rong [4 ]
Uemura, Yasushi [4 ]
Yamashita, Hiromi [1 ]
Matsuoka, Yoshikazu [1 ]
Shirouzu, Yasumasa [1 ]
Fujioka, Tatsuya [1 ]
Hattori, Fumiyuki [1 ]
Ogata, Hiroaki [5 ]
Sakashita, Akiko [5 ]
Honda, Hirokazu [2 ]
Hitomi, Hirofumi [1 ]
机构
[1] Kansai Med Univ, Dept iPS Stem Cell Regenerat Med, Osaka, Japan
[2] Showa Univ, Sch Med, Dept Med, Div Nephrol, 1-5-8 Hatanodai,Shinagawa, Tokyo 1428555, Japan
[3] Osaka Dent Univ, Fac Dent, Dept Pharmacol, Osaka, Japan
[4] Natl Canc Ctr, Exploratory Oncol Res & Clin Trial Ctr, Div Canc Immunotherapy, Chiba, Japan
[5] Showa Univ, Northern Yokohama Hosp, Dept Internal Med, Yokohama, Kanagawa, Japan
基金
日本学术振兴会;
关键词
Glial cells missing 2; Pluripotent stem cells; Parathyroid; RECEPTOR EXPRESSION; SWITCH; ENDODERM; 3RD;
D O I
10.1016/j.tice.2024.102634
中图分类号
R602 [外科病理学、解剖学]; R32 [人体形态学];
学科分类号
100101 ;
摘要
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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页数:8
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