Single-cell analysis of the developing human ovary defines distinct insights into ovarian somatic and germline progenitors

Sissy E Wamaitha; Xichen Nie; Erica C Pandolfi; Xiaoyan Wang; Yifan Yang; Jan-Bernd Stukenborg; Bradley R Cairns; Jingtao Guo; Amander T Clark

doi:10.1016/j.devcel.2023.07.014

Single-cell analysis of the developing human ovary defines distinct insights into ovarian somatic and germline progenitors

Dev Cell. 2023 Oct 23;58(20):2097-2111.e3. doi: 10.1016/j.devcel.2023.07.014. Epub 2023 Aug 14.

Authors

Sissy E Wamaitha¹, Xichen Nie², Erica C Pandolfi¹, Xiaoyan Wang³, Yifan Yang⁴, Jan-Bernd Stukenborg⁴, Bradley R Cairns⁵, Jingtao Guo⁶, Amander T Clark⁷

Affiliations

¹ Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90033, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
² Division of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT 84112, USA; Howard Hughes Medical Institute, Department of Oncological Sciences and Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
³ State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
⁴ NORDFERTIL Research Laboratory Stockholm, Childhood Cancer Research Unit, Bioclinicum J9:30, Department of Women's and Children's Health, Karolinska Institutet and Karolinska University Hospital, Solna 17164, Sweden.
⁵ Howard Hughes Medical Institute, Department of Oncological Sciences and Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
⁶ Division of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT 84112, USA; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: jingtao.guo@ioz.ac.cn.
⁷ Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90033, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: clarka@ucla.edu.

PMID: 37582368
PMCID: PMC10615783 (available on 2024-10-23)
DOI: 10.1016/j.devcel.2023.07.014

Abstract

Formation of either an ovary or a testis during human embryonic life is one of the most important sex-specific events leading to the emergence of secondary sexual characteristics and sex assignment of babies at birth. Our study focused on the sex-specific and sex-indifferent characteristics of the prenatal ovarian stromal cells, cortical cords, and germline, with the discovery that the ovarian mesenchymal cells of the stroma are transcriptionally indistinguishable from the mesenchymal cells of the testicular interstitium. We found that first-wave pre-granulosa cells emerge at week 7 from early supporting gonadal cells with stromal identity and are spatially defined by KRT19 levels. We also identified rare transient state f0 spermatogonia cells within the ovarian cords between weeks 10 and 16. Taken together, our work illustrates a unique plasticity of the embryonic ovary during human development.

Keywords: germ cells; germ line; granulosa cells; ovary development; pre-granulosa cells; testis development.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Female
Germ Cells
Gonads*
Humans
Infant, Newborn
Male
Ovary*
Single-Cell Analysis
Testis

Abstract

Publication types

MeSH terms

Grants and funding