Differentiation of primordial germ cells from premature ovarian insufficiency-derived induced pluripotent stem cells

Stem Cell Research & Therapy

Lixia He¹  Kefei Gao¹  Cijun Shuai²  Shufang Ding³  Sheng Yang³  Shuping Peng⁴  Shiwei He⁴ 

[1] Department of Obstetrics and Gynecology, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy;State Key Laboratory of High Performance Complex Manufacturing, Central South University;The Center of Reproduction Medicine, The University of Hong Kong-Shenzhen Hospital;The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, the Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and Cancer Research Institute, Xiangya Hospital, Central South University;

关键词: Premature ovarian insufficient;    Induced pluripotent stem cells;    Primordial germ cells;    Reprogramming;    Differentiation;   

DOI  :  10.1186/s13287-019-1261-6

来源: DOAJ

【 摘 要 】

Abstract Background Premature ovarian insufficiency (POI) is a common disease in reproductive women. The pathogenesis of POI is not clear, although it is known that it involves the disorder of oocyte differentiation and development. The introduction of reprogramming human somatic cells into induced pluripotent stem cells (iPSCs) offers a unique opportunity to study many aspects of POI from cell differentiation in vitro that could ultimately lead to novel drug development and testing to help treat the disorder. Methods The fibroblasts from POI patients, including fragile X syndrome, abnormal karyotype (45, X; 45, X/46, XX; 45, XO and 47, XXX), and the gene mutation (FIGLA and GDF9) were reprogrammed to pluripotency status by retroviral transduction using defined factors. The morphology, growth characteristics, gene expression profiles, epigenetic status, and in vitro and in vivo differentiation potential of the POI-1-iPSCs (from fragile X syndrome) were analyzed. Then, POI-1-iPSCs were induced to differentiation into primordial germ cells (PGCs) with DNA methyltransferase inhibitors. Results The iPSCs were successfully generated from POI patients’ fibroblasts. The formed iPS clones have the same characteristics of human ESCs. POI-1-iPSCs were successfully generated with germline competence. The POI-1-iPSCs, with genotypes of fragile X syndrome, can be induced to differentiation into PGCs with high efficiency under our culture system by DNA demethylation. This study proved that disease-specific iPSC lines derived from POI patients could be generated and successfully differentiated into PGCs. Conclusions We established some novel, systemic cell models for the studying of the pathogenesis of POI patients. Second, DNA demethylation may accelerate the induction of human PGCs from iPSCs in vitro and the conclusion needs further exploration. This represents an important step in the novel approach for the study of the pathophysiology and potential egg resource for POI patients.

【 授权许可】

Unknown