Specification of human germ cell fate with enhanced progression capability supported by hindgut organoids

João Pedro Alves-Lopes; Frederick C K Wong; Walfred W C Tang; Wolfram H Gruhn; Navin B Ramakrishna; Geraldine M Jowett; Kirsi Jahnukainen; M Azim Surani

doi:10.1016/j.celrep.2022.111907

Specification of human germ cell fate with enhanced progression capability supported by hindgut organoids

Cell Rep. 2023 Jan 31;42(1):111907. doi: 10.1016/j.celrep.2022.111907. Epub 2023 Jan 5.

Authors

João Pedro Alves-Lopes¹, Frederick C K Wong², Walfred W C Tang², Wolfram H Gruhn², Navin B Ramakrishna³, Geraldine M Jowett², Kirsi Jahnukainen⁴, M Azim Surani⁵

Affiliations

¹ Wellcome/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK; Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK; NORDFERTIL Research Lab Stockholm, Childhood Cancer Research Unit, J9:30, Department of Women's and Children's Health, Karolinska Institutet and Karolinska University Hospital, Visionsgatan 4, Solna, 17164 Stockholm, Sweden. Electronic address: joao.pedro.lopes@ki.se.
² Wellcome/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK; Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
³ Wellcome/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK; Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK; Genome Institute of Singapore, A(∗)STAR, Biopolis, Singapore 138672, Singapore.
⁴ NORDFERTIL Research Lab Stockholm, Childhood Cancer Research Unit, J9:30, Department of Women's and Children's Health, Karolinska Institutet and Karolinska University Hospital, Visionsgatan 4, Solna, 17164 Stockholm, Sweden; New Children's Hospital, Paediatric Research Centre, University of Helsinki and Helsinki University Hospital, Pl 281, 00029 Helsinki, Finland.
⁵ Wellcome/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK; Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK. Electronic address: as10021@cam.ac.uk.

PMID: 36640324
DOI: 10.1016/j.celrep.2022.111907

Abstract

Human primordial germ cells (hPGCs), the precursors of sperm and eggs, are specified during weeks 2-3 after fertilization. Few studies on ex vivo and in vitro cultured human embryos reported plausible hPGCs on embryonic day (E) 12-13 and in an E16-17 gastrulating embryo. In vitro, hPGC-like cells (hPGCLCs) can be specified from the intermediary pluripotent stage or peri-gastrulation precursors. Here, we explore the broad spectrum of hPGCLC precursors and how different precursors impact hPGCLC development. We show that resetting precursors can give rise to hPGCLCs (rhPGCLCs) in response to BMP. Strikingly, rhPGCLCs co-cultured with human hindgut organoids progress at a pace reminiscent of in vivo hPGC development, unlike those derived from peri-gastrulation precursors. Moreover, rhPGCLC specification depends on both EOMES and TBXT, not just on EOMES as for peri-gastrulation hPGCLCs. Importantly, our study provides the foundation for developing efficient in vitro models of human gametogenesis.

Keywords: CP: Stem cell research; Hindgut organoid; Primordial germ cell; Primordial germ cell-like cell precursor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Differentiation
Embryo, Mammalian
Germ Cells*
Humans
Male
Organoids
Semen*

Abstract

Publication types

MeSH terms

Grants and funding