类有机物
胚胎干细胞
干细胞
细胞生物学
生物
细胞分化
甲状旁腺主细胞
转染
定向微分
甲状旁腺激素
细胞培养
分子生物学
内科学
诱导多能干细胞
医学
钙
基因
遗传学
生物化学
作者
Ge Wang,Yaying Du,Xiaoqing Cui,Tao Xu,Hanning Li,Menglu Dong,Wei Li,Yajie Li,Wenjun Cai,Jia Xu,Shuyu Li,Xue Yang,Yonglin Wu,Hong Chen,Xueying Li
摘要
Abstract Differentiation of human embryonic stem cells (hESCs) into human embryonic stem cells‐derived parathyroid‐like cells (hESC‐PT) has clinical significance in providing new therapies for congenital and acquired parathyroid insufficiency conditions. However, a highly reproducible, well‐documented 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‐like 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‐derived parathyroid organoids. The new protocol enabled hESCs to differentiate into hESC‐PT. HESC‐PT cells expressed PTH, GCM2 and CaSR proteins, low extracellular calcium culture could stimulate hESC‐PT cells to secrete PTH. hESC‐PT cells overexpressing GCM2 protein secreted PTH earlier than their counterpart hESC‐PT cells. Compared with the two‐dimensional cell culture environment, hESCs‐derived parathyroid organoids secreted more PTH. Both GCM2 lentiviral transfection and three‐dimensional cultures could make hESC‐PT cells functionally close to human parathyroid cells. Our study demonstrated that hESCs could differentiate into hESC‐PT in vitro, which paves the road for applying the technology to treat hypoparathyroidism and introduces new approaches in the field of regenerative medicine.
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