Generation of ovarian follicles from mouse pluripotent stem cells

• Published in: Science (American Association for the Advancement of Science) Vol. 373; no. 6552
• Main Authors: Yoshino, Takashi, Suzuki, Takahiro, Nagamatsu, Go, Yabukami, Haruka, Ikegaya, Mika, Kishima, Mami, Kita, Haruka, Imamura, Takuya, Nakashima, Kinichi, Nishinakamura, Ryuichi, Tachibana, Makoto, Inoue, Miki, Shima, Yuichi, Morohashi, Ken-Ichirou, Hayashi, Katsuhiko
• Format: Journal Article
• Language: English
• Published: United States The American Association for the Advancement of Science 16.07.2021
• Subjects: Animals; Cell culture; Cell Culture Techniques; Cell Differentiation; Differentiation (biology); Embryo cells; Embryogenesis; Embryonic Development; Endangered animals; Endangered species; Environment; Environments; Epithelium; Ethical standards; Female; Fertilization; Fertilization in Vitro; Fetuses; Follicles; Gametes; Gametocytes; Gametogenesis; Gene expression; Germ cells; Gonads; In vitro methods and tests; In vivo methods and tests; Individualized Instruction; Mammals; Meiosis; Mesoderm; Mesoderm - cytology; Mesoderm - physiology; Mice; Mice, Inbred ICR; Mouse Embryonic Stem Cells - cytology; Mouse Embryonic Stem Cells - physiology; Offspring; Oocytes; Oocytes - cytology; Oocytes - physiology; Oogenesis; Organs; Ovarian Follicle - cytology; Ovarian Follicle - embryology; Ovarian Follicle - physiology; Ovaries; Reporter gene; Reproduction; Reproductive organs; RNA-Seq; Somatic cells; Species; Stem cells; Steroidogenic Factor 1 - genetics; Steroidogenic Factor 1 - metabolism; Tissues; Transcription; Transcriptome
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.abe0237

Oocytes mature in a specialized fluid-filled sac, the ovarian follicle, which provides signals needed for meiosis and germ cell growth. Methods have been developed to generate functional oocytes from pluripotent stem cell-derived primordial germ cell-like cells (PGCLCs) when placed in culture with embryonic ovarian somatic cells. In this study, we developed culture conditions to recreate the stepwise differentiation process from pluripotent cells to fetal ovarian somatic cell-like cells (FOSLCs). When FOSLCs were aggregated with PGCLCs derived from mouse embryonic stem cells, the PGCLCs entered meiosis to generate functional oocytes capable of fertilization and development to live offspring. Generating functional mouse oocytes in a reconstituted ovarian environment provides a method for in vitro oocyte production and follicle generation for a better understanding of mammalian reproduction.