Granulosa cell-derived induced pluripotent stem cells exhibit pro-Trophoblastic differentiation potential

Ching Yu Chuang, Mei Chi Huang, Hsin Fu Chen, Li Hui Tseng, Chun Ying Yu, Lee Stone, Hsiang Po Huang, Hong Nerng Ho, Hung Chih Kuo

研究成果: 雜誌貢獻文章同行評審

3 引文 斯高帕斯(Scopus)

摘要

Introduction: Human induced pluripotent stem cells (hiPSCs) have been derived from various somatic cell types. Granulosa cells, a group of cells which surround oocytes and are obtained from the (normally discarded) retrieved egg follicles of women undergoing infertility treatment, are a possible cell source for induced pluripotent stem cell (iPSC) generation. Here, we explored the possibility of using human granulosa cells as a donor cell type for iPSC reprogramming, and compared granulosa cell-derived iPSCs (iGRAs) with those derived from other cell sources, to determine the potential ability of iGRA differentiation. Methods: Granulosa cells were collected from egg follicles retrieved from women undergoing infertility treatment. After short-Term culture, the granulosa cells derived from different patients were mixed in culture, and infected with retroviruses encoding reprogramming factors. The resulting iPSC clones were selected and subjected to microsatellite DNA analysis to determine their parental origin. IGRAs were subjected to RT-PCR, immunofluorescence staining, and in vitro and in vivo differentiation assays to further establish their pluripotent characteristics. Results: Microsatellite DNA analysis was used to demonstrate that hiPSCs with different parental origins can be simultaneously reprogrammed by retroviral transfection of a mixed human granulosa cell population obtained from multiple individuals. The iGRAs resemble human embryonic stem cells (hESCs) in many respects, including morphological traits, growth requirements, gene and marker expression profiles, and in vitro and in vivo developmental propensities. We also demonstrate that the iGRAs express low levels of NLRP2, and differentiating iGRAs possess a biased differentiation potential toward the trophoblastic lineage. Although NLRP2 knockdown in hESCs promotes trophoblastic differentiation of differentiating hESCs, it does not result in exit from pluripotency. These results imply that NLRP2 may play a role in regulating the trophoblastic differentiation of human pluripotent stem cells. Conclusions: These findings provide a means of generating iPSCs from multiple granulosa cell populations with different parental origins. The ability to generate iPSCs from granulosa cells not only enables modeling of infertility-Associated disease, but also provides a means of identifying potential clinical interventions through iPSC-based drug screening.
原文英語
文章編號14
期刊Stem Cell Research and Therapy
6
發行號1
DOIs
出版狀態已發佈 - 二月 27 2015
對外發佈

ASJC Scopus subject areas

  • 醫藥(雜項)
  • 分子醫學
  • 生物化學、遺傳與分子生物學(雜項)
  • 細胞生物學

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