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

iScience (Jan 2021)

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

Affiliations

Danny C.W. Yu: Department of Obstetrics and Gynecology, College of Medicine and the Hospital, National Taiwan University, Taipei, Taiwan; Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei, Taiwan; Institute of Immunotherapy, Fujian Medical University, Fujian, China; Aging and Disease Prevention Research Center, and Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan
Fang-Chun Wu: Department of Obstetrics and Gynecology, College of Medicine and the Hospital, National Taiwan University, Taipei, Taiwan; Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei, Taiwan
Chia-Eng Wu: Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan
Lu-Ping Chow: Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
Hong-Nerng Ho: Department of Obstetrics and Gynecology, College of Medicine and the Hospital, National Taiwan University, Taipei, Taiwan; Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan
Hsin-Fu Chen: Department of Obstetrics and Gynecology, College of Medicine and the Hospital, National Taiwan University, Taipei, Taiwan; Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei, Taiwan; Corresponding author

Journal volume & issue: Vol. 24, no. 1
p. 102003

Abstract

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Summary: 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 (DDX4ec 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 DDX4ec PGCLCs and plays a crucial role in germ cell migration. By co-culturing DDX4ec 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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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