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Processing Bodies Restrict the Specification of Human Primordial Germ Cells

ABSTRACT: Precursor cells gradually become restricted in their fates during development by the combined functions of cell fate “specifiers” and “restrictors”, the balancing of which determines the correct cell numbers for specific lineages. However, little is known about the regulators restricting the specification of primordial germ cells (PGCs), the precursors of germline for perpetuating genetic and epigenetic information from parents to offspring. We identified the processing body (P-body) component 4E-T (also called EIF4ENIF1) as a critical restrictor that suppresses the specification of PGC-like cells from human embryonic stem cells (hESCs). The phase separation nature of 4E-T and P-bodies is important for stabilizing the mRNAs of OTX2, which restricts the entry of germline as a transcriptional regulator. Mechanistically, 4E-T proteins within P-bodies sequester the m6A reader IGF2BP1, which binds to the m6A-modified OTX2 mRNAs for transporting to ribosomes for active translation. In summary, we reveal the novel function of membraneless organelle P-bodies as a key site for sorting m6A-modified mRNAs for translation, which in turn is involved in the regulation of cell fate during development.

ORGANISM(S): Homo sapiens

PROVIDER: GSE287293 | GEO | 2026/09/18

REPOSITORIES: GEO

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IGF2BP1 stabilizes OTX2 mRNA in an m6A-dependent manner to restrict human germ cell fate by repressing TFAP2C

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