Human pluripotent stem cell-derived DDX4 and KRT-8 positive cells participate in ovarian follicle-like structure formation

Danny C W Yu; Fang-Chun Wu; Chia-Eng Wu; Lu-Ping Chow; Hong-Nerng Ho; Hsin-Fu Chen

doi:10.1016/j.isci.2020.102003

Human pluripotent stem cell-derived DDX4 and KRT-8 positive cells participate in ovarian follicle-like structure formation

iScience. 2020 Dec 29;24(1):102003. doi: 10.1016/j.isci.2020.102003. eCollection 2021 Jan 22.

Authors

Danny C W Yu^{1

2

3

4}, Fang-Chun Wu^{1

2}, Chia-Eng Wu⁵, Lu-Ping Chow⁶, Hong-Nerng Ho^{1

2

5}, Hsin-Fu Chen^{1

2}

Affiliations

¹ Department of Obstetrics and Gynecology, College of Medicine and the Hospital, National Taiwan University, Taipei, Taiwan.
² Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei, Taiwan.
³ Institute of Immunotherapy, Fujian Medical University, Fujian, China.
⁴ Aging and Disease Prevention Research Center, and Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan.
⁵ Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan.
⁶ Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.

Abstract

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 DDX4^ec 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.

Keywords: Cell Biology; Developmental Biology; Molecular Biology; Stem Cell Research.