High resolution multi-scale profiling of embryonic germ cell-like cell derivation reveals pluripotent state transitions in humans.

Stucchi S, Sepulveda-Rincon LP, Dion C, Matassa G, Valenti A, Cheroni C, Vitriolo A, Prazzoli F, Young G, Rigoli MT, Nagni R, Ciprietti M, Muda B, Heckhausen Z, Hajkova P, Caporale N, Testa G, Leitch HG
Stem cell reports · 2026 · doi:10.1016/j.stemcr.2025.102746 · PMID:41418783 · PMC12925952
Lab / animal OA: gold
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Abstract

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.

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organisms 56
rodents human humans human mus sp. human human humans human humans human transgenic mice transgenic mice transgenic mice rattus sp. zitter rats humans human mus sp. human human transgenic mice human human transgenic mice human human mus sp. human transgenic mice transgenic mice human human transgenic mice human transgenic mice human human mus sp. transgenic mice transgenic mice human transgenic mice human mammals mus sp. humans humans mus sp. human humans humans human human human human
chemicals 7
penicillin streptomycin forskolin retinoic acid methyl 5-methylcytosine methylcytosine

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