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However, a highly reproducible, well\u2010documented method for parathyroid differentiation remains unavailable. By imitating the natural process of parathyroid embryonic development, we proposed a new hypothesis about the in vitro differentiation of parathyroid\u2010like cells. Transcriptome, differentiation marker protein detection and parathyroid hormone (PTH) secretion assays were performed after the completion of differentiation. To optimize the differentiation protocol and further improve the differentiation rate, we designed glial cells missing transcription factor 2 (GCM2) overexpression lentivirus transfection assays and constructed hESCs\u2010derived parathyroid organoids. The new protocol enabled hESCs to differentiate into hESC\u2010PT. HESC\u2010PT cells expressed PTH, GCM2 and CaSR proteins, low extracellular calcium culture could stimulate hESC\u2010PT cells to secrete PTH. hESC\u2010PT cells overexpressing GCM2 protein secreted PTH earlier than their counterpart hESC\u2010PT cells. Compared with the two\u2010dimensional cell culture environment, hESCs\u2010derived parathyroid organoids secreted more PTH. Both GCM2 lentiviral transfection and three\u2010dimensional cultures could make hESC\u2010PT cells functionally close to human parathyroid cells. Our study demonstrated that hESCs could differentiate into hESC\u2010PT in vitro, which paves the road for applying the technology to treat hypoparathyroidism and introduces new approaches in the field of regenerative medicine.<\/jats:p>","DOI":"10.1111\/cpr.13634","type":"journal-article","created":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T07:30:49Z","timestamp":1710747049000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Directed differentiation of human embryonic stem cells into parathyroid cells and establishment of parathyroid organoids"],"prefix":"10.1111","volume":"57","author":[{"given":"Ge","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan 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