Single-cell roadmap of human gonadal development

Luz Garcia-Alonso, Valentina Lorenzi, Cecilia Icoresi Mazzeo, João Pedro Alves-Lopes, Kenny Roberts, Carmen Sancho-Serra, Justin Engelbert, Magda Marečková, Wolfram H. Gruhn, Rachel A. Botting, Tong Li, Berta Crespo, Stijn Dongen, Vladimir Yu Kiselev, Elena Prigmore, Mary Herbert, Ashley Moffett, Alain Chédotal, Omer Ali Bayraktar, Azim Surani, Muzlifah Haniffa and Roser Vento-Tormo ()
Additional contact information
Luz Garcia-Alonso: Wellcome Sanger Institute
Valentina Lorenzi: Wellcome Sanger Institute
Cecilia Icoresi Mazzeo: Wellcome Sanger Institute
João Pedro Alves-Lopes: University of Cambridge
Kenny Roberts: Wellcome Sanger Institute
Carmen Sancho-Serra: Wellcome Sanger Institute
Justin Engelbert: Newcastle University
Magda Marečková: Wellcome Sanger Institute
Wolfram H. Gruhn: University of Cambridge
Rachel A. Botting: Newcastle University
Tong Li: Wellcome Sanger Institute
Berta Crespo: University College London
Stijn Dongen: Wellcome Sanger Institute
Vladimir Yu Kiselev: Wellcome Sanger Institute
Elena Prigmore: Wellcome Sanger Institute
Mary Herbert: Newcastle University
Ashley Moffett: University of Cambridge
Alain Chédotal: Sorbonne Université, INSERM, CNRS, Institut de la Vision
Omer Ali Bayraktar: Wellcome Sanger Institute
Azim Surani: University of Cambridge
Muzlifah Haniffa: Wellcome Sanger Institute
Roser Vento-Tormo: Wellcome Sanger Institute

Nature, 2022, vol. 607, issue 7919, 540-547

Abstract: Abstract Gonadal development is a complex process that involves sex determination followed by divergent maturation into either testes or ovaries1. Historically, limited tissue accessibility, a lack of reliable in vitro models and critical differences between humans and mice have hampered our knowledge of human gonadogenesis, despite its importance in gonadal conditions and infertility. Here, we generated a comprehensive map of first- and second-trimester human gonads using a combination of single-cell and spatial transcriptomics, chromatin accessibility assays and fluorescent microscopy. We extracted human-specific regulatory programmes that control the development of germline and somatic cell lineages by profiling equivalent developmental stages in mice. In both species, we define the somatic cell states present at the time of sex specification, including the bipotent early supporting population that, in males, upregulates the testis-determining factor SRY and sPAX8s, a gonadal lineage located at the gonadal–mesonephric interface. In females, we resolve the cellular and molecular events that give rise to the first and second waves of granulosa cells that compartmentalize the developing ovary to modulate germ cell differentiation. In males, we identify human SIGLEC15+ and TREM2+ fetal testicular macrophages, which signal to somatic cells outside and inside the developing testis cords, respectively. This study provides a comprehensive spatiotemporal map of human and mouse gonadal differentiation, which can guide in vitro gonadogenesis.

Date: 2022
References: Add references at CitEc
Citations: View citations in EconPapers (4)

Downloads: (external link)
https://www.nature.com/articles/s41586-022-04918-4 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:607:y:2022:i:7919:d:10.1038_s41586-022-04918-4

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-022-04918-4

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().