The Induction of Parathyroid Cell Differentiation from Human Induced Pluripotent Stem Cells Promoted Via TGF-α/EGFR Signaling
Authors:
- Ryusuke NakatsukaRNRyusuke Nakatsuka
- Tadashi KatoTKTadashi Kato
- Rong ZhangRZRong Zhang
- Yasushi UemuraYUYasushi Uemura
- Yuka SasakiYSYuka Sasaki
- Yoshikazu MatsuokaYMYoshikazu Matsuoka
- Yasumasa ShirouzuYSYasumasa Shirouzu
- Tatsuya FujiokaTFTatsuya Fujioka
- Hiromi YamashitaHYHiromi Yamashita
- Fumiyuki HattoriFHFumiyuki Hattori
- Tadashige NozakiTNTadashige Nozaki
- Hiroaki OgataHOHiroaki Ogata
- 1 November 2023
- journal article
- research article
- Published by SAGE Publications in Stem Cells and Development
- Vol. 32 (21-22) , 670-680
Abstract
The parathyroid gland plays an essential role in mineral and bone metabolism. A cultivation for physiological human parathyroid cells has yet to be established and the method by which parathyroid cells differentiate from pluripotent stem cells remains uncertain. Therefore, it has been hard to clarify the mechanisms underlying the onset of parathyroid disorders, such as hyperparathyroidism. Here, we developed a new method of parathyroid cell differentiation from human induced pluripotent stem (iPS) cells. The parathyroid cell differentiation occurred in accordance with embryologic development. The differentiated cells, which expressed parathyroid hormone, adopted a unique cell aggregation similar to the parathyroid gland. In addition, these differentiated cells were identified as calcium-sensing receptor (CaSR)/epithelial cell adhesion molecule (EpCAM) double-positive cells. Interestingly, stimulation with transforming growth factor-α (TGF-α), which is considered a causative molecule of parathyroid hyperplasia, increased the CaSR/EpCAM double-positive cells, but this effect was suppressed by erlotinib, which is an epidermal growth factor receptor (EGFR) inhibitor. These results suggest that TGF-α/EGFR signaling promotes parathyroid cell differentiation from iPS cells in a similar manner to parathyroid hyperplasia.Keywords
This publication has 29 references indexed in Scilit:
- Analysis of SOX2-Expressing Cell Populations Derived from Human Pluripotent Stem CellsStem Cell Reports, 2013
- Highly Efficient Generation of Human Hepatocyte–Like Cells From Induced Pluripotent Stem CellsHepatology, 2009
- The Cell Cycle and Myc Intersect with Mechanisms that Regulate Pluripotency and ReprogrammingCell Stem Cell, 2009
- Activator Protein 2α Mediates Parathyroid TGF-α Self-Induction in Secondary HyperparathyroidismJournal of the American Society of Nephrology, 2008
- Expression of the semaphorins Sema 3D and Sema 3F in the developing parathyroid and thymusDevelopmental Dynamics, 2008
- Distinct subsets of human invariant NKT cells differentially regulate T helper responses via dendritic cellsEuropean Journal of Immunology, 2008
- Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined FactorsCell, 2007
- Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined FactorsCell, 2006
- Pathogenic mechanisms for parathyroid hyperplasiaKidney International, 2006
- Regulation of PTH synthesis and secretion relevant to the management of secondary hyperparathyroidism in chronic kidney diseaseKidney International, 2005