Journal
ISCIENCE
Volume 24, Issue 1, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.isci.2020.102003
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Funding
- National Science Council of the Republic of China [NSC 99-3111-B-002-009, NSC 99-3111-B-002-007, NSC 100-2321-B-002-072, NSC 101-2321-B-002-036, MOST 102-2321-B-002-092-MY3, MOST 104-2321-B-002-043]
- National Taiwan University Hospital [MG 273]
- Foundation for Postdoctoral Science Exchange Program of Two Sides of Strait [245094]
- MOST, Taiwan
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This study demonstrated the induction of hPSCs into DDX4(ec) PGCLCs and their further development into ovarian follicle-like structures by co-culturing with human granulosa cells in a xenograft mice model. These findings offer a potential new strategy for treating germ cell-associated issues of infertility.
Understanding the mechanisms of human pluripotent stem cells (hPSCs) specification, development and differentiation to gametes are useful for elucidating the causes of infertility and potential treatment. This study aims to examine whether hPSCs can be induced to DDX4 extracellularly expressing primordial germ cell-like cells (DDX4(ec) PGCLCs) and further into ovarian follicle stage in a combined in vitro and in vivo model. The transcriptional signatures show that these DDX4ec PGCLCs are characteristic of PGCs and express ovarian folliculogenesis markers. We also verify that keratin (KRT)-8 is highly expressed in the DDX4(ec) PGCLCs and plays a crucial role in germ cell migration. By co-culturing DDX4(ec) PGCLCs with human granulosa cells (GCs), these cells are further induced into ovarian follicle-like structures in a xenograft mice model. This approach can in the future design practical strategies for treating germ cell-associated issues of infertility.
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