Emerging principles and models of human primordial germ cell development
Navin B Ramakrishna1, João Pedro Alves-Lopes2, Wolfram H Gruhn3,4,5
1Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), 60 Biopolis Street, Genome, Singapore 138672, Republic of Singapore.
Development (Cambridge, England)
|September 11, 2025
Summary
Human primordial germ cells (hPGCs) undergo critical epigenetic reprogramming and microenvironmental interactions during early embryonic development. Understanding these processes is key for future gametogenesis and in vitro models.
Area of Science:
- Developmental Biology
- Stem Cell Biology
- Reproductive Biology
Background:
- Primordial germ cells (hPGCs) are crucial for human reproduction, initiating gamete formation.
- hPGCs undergo significant epigenetic reprogramming and fitness selection during the first trimester.
- The microenvironment influencing hPGC development in human embryos is not fully understood.
Purpose of the Study:
- To review microenvironmental and epigenetic changes during early human hPGC development (up to week 10).
- To examine current stem cell-based model systems for hPGC differentiation.
- To highlight mechanistic insights gained from these models for human in vitro gametogenesis.
Main Methods:
- Review of recent transcriptomic and epigenetic profiling studies in human embryos.
- Integration of data from non-human primate models.
- Analysis of pluripotent stem cell-based systems modeling hPGC differentiation.
Main Results:
- Identification of key signalling cues and regulatory mechanisms governing hPGC specification, migration, and gonadal development.
- Characterization of epigenetic reprogramming dynamics in early hPGCs.
- Validation of stem cell models for studying hPGC development.
Conclusions:
- Early embryonic microenvironments and epigenetic modifications are fundamental to hPGC development.
- Stem cell models provide powerful platforms for mechanistic studies of hPGCs.
- Advancements facilitate efforts towards establishing human in vitro gametogenesis.
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