High resolution multi-scale profiling of embryonic germ cell-like cell derivation reveals pluripotent state transitions in humans
Primordial germ cells (PGCs) are the embryonic precursors of the gametes. In rodents, PGCs readily form self-renewing embryonic germ cell (EGC) lines in vitro. Although human PGCs undergo a similar conversion during germ cell tumorigenesis, no comparable in vitro system has yet been established in humans. Here we report that hPGC-like cells (hPGCLCs) undergo conversion to human EGC-like cells (hEGCLCs) using the inductive signals previously identified in mice. This feeder-free culture system allows efficient derivation of hEGCLCs that are transcriptionally similar to human induced pluripotent stem cells and can give rise to hPGCLCs once more demonstrating the interconvertibility of pluripotent states. This is also evident at the chromatin level, as the initial DNA demethylation that occurs in hPGCLCs is reversed in hEGCLCs. This new in vitro model provides a highly tractable system to study human pluripotent and early developmental transitions, including those driving germ cell tumorigenesis and epigenetic inheritance.
Authors
- Marco Tullio Rigoli (ORCID: https://orcid.org/0000-0002-0740-0117)
- Petra Hájková (ORCID: https://orcid.org/0000-0003-4145-1468)
- Lessly P. Sepulveda-Rincon (ORCID: https://orcid.org/0000-0001-8654-7362)
- Martina Ciprietti (ORCID: https://orcid.org/0000-0001-7209-7604)
- Zoe Heckhausen (ORCID: https://orcid.org/0000-0003-0085-2492)
- Alessandro Vitriolo (ORCID: https://orcid.org/0000-0002-1462-8064)
- Cristina Cheroni (ORCID: https://orcid.org/0000-0002-0832-2333)
- Camille Dion (ORCID: https://orcid.org/0000-0003-1299-1772)
- Harry G. Leitch (ORCID: https://orcid.org/0000-0002-3486-8962)
- Nicolò Caporale (ORCID: https://orcid.org/0000-0001-8097-4320)
- S. Stucchi (ORCID: https://orcid.org/0000-0002-9426-1601)
- George Young (ORCID: https://orcid.org/0000-0001-7907-6427)
- Giuseppe Testa (ORCID: https://orcid.org/0000-0002-9104-0918)
- Alessia Valenti
- Gaja Matassa
- Benedetta Muda
- Filippo Prazzoli
- Riccardo Nagni
Institutions
- University of Milan (IT)
- Human Technopole (IT)
- MRC London Institute of Medical Sciences (GB)
- European Institute of Oncology (IT)
Publication Details
- Journal
- Stem Cell Reports
- Published
- 2025-12-19
- DOI
- https://doi.org/10.1016/j.stemcr.2025.102746
- Primary Topic
- Pluripotent Stem Cells Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00