IGF2BP1 restricts the induction of human primordial germ cell fate in an m<sup>6</sup>A-dependent manner.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 40436019.
- Also identified by DOI 10.1016/j.stem.2025.05.001.
- No licence information is recorded for this record.
- Because redistribution is not established, this page shows the abstract only. Follow the links below for the full text.
Abstract
Primordial germ cells (PGCs) are specified early during embryogenesis and establish the germ cell lineage for transmitting genetic and epigenetic information from parents to offspring. However, whether N<sup>6</sup>-methyladenosine (m<sup>6</sup>A)-mediated epigenetic regulation is involved in the specification of PGCs remains elusive. In this study, we report that a knockout of m<sup>6</sup>A writers or overexpression of m<sup>6</sup>A erasers leads to an increased percentage of human PGC-like cells (hPGCLCs) induced from embryonic stem cells using a 3D aggregate system. We identify the m<sup>6</sup>A reader IGF2BP1 as the key factor for restricting hPGCLC fate induction by stabilizing OTX2 mRNAs in an m<sup>6</sup>A-dependent manner. In turn, OTX2 protein suppresses the function of TFAP2C via histone variant MacroH2A.1 during germ cell lineage specification. We also observe a similar role of Igf2bp1 in zebrafish in the induction of PGC fate. In summary, we identify an m<sup>6</sup>A-IGF2BP1-OTX2-MacroH2A.1-TFAP2C signaling axis that restricts the specification of human germ cell fate.
Medical subject headings
- RNA-Binding Proteins
- Germ Cells
- Adenosine