PUBLICATION
IGF2BP1 restricts the induction of human primordial germ cell fate in an m6A-dependent manner
- Authors
- Zhang, J., Gu, Y., Tong, L., Feng, B., Dong, S., Shao, Q., Chen, Y., Tu, H., Wang, Z., Wang, Y., Li, X., Yu, H., Lin, Z., Wang, X., Li, Z., Ai, Z., Xiang, Y., Jiang, Z., Jin, Z., Li, Z., Chen, Y., Shen, Z., Huang, C., Liu, J., Liu, J., Xu, P., Yu, Y., Xia, P., Liang, H., Huang, H., Chen, D.
- ID
- ZDB-PUB-250529-5
- Date
- 2025
- Source
- Cell Stem Cell : (Journal)
- Registered Authors
- Keywords
- IGF2BP1, MacroH2A.1, OTX2, PGC restrictors, TFAP2C, m(6)A modification, primordial germ cells
- MeSH Terms
-
- Zebrafish
- Transcription Factor AP-2/metabolism
- Cell Differentiation
- Adenosine*/analogs & derivatives
- Adenosine*/metabolism
- Histones/metabolism
- Animals
- Humans
- Cell Lineage
- Germ Cells*/cytology
- Germ Cells*/metabolism
- RNA-Binding Proteins*/genetics
- RNA-Binding Proteins*/metabolism
- PubMed
- 40436019 Full text @ Cell Stem Cell
Citation
Zhang, J., Gu, Y., Tong, L., Feng, B., Dong, S., Shao, Q., Chen, Y., Tu, H., Wang, Z., Wang, Y., Li, X., Yu, H., Lin, Z., Wang, X., Li, Z., Ai, Z., Xiang, Y., Jiang, Z., Jin, Z., Li, Z., Chen, Y., Shen, Z., Huang, C., Liu, J., Liu, J., Xu, P., Yu, Y., Xia, P., Liang, H., Huang, H., Chen, D. (2025) IGF2BP1 restricts the induction of human primordial germ cell fate in an m6A-dependent manner. Cell Stem Cell. :.
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 N6-methyladenosine (m6A)-mediated epigenetic regulation is involved in the specification of PGCs remains elusive. In this study, we report that a knockout of m6A writers or overexpression of m6A 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 m6A reader IGF2BP1 as the key factor for restricting hPGCLC fate induction by stabilizing OTX2 mRNAs in an m6A-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 m6A-IGF2BP1-OTX2-MacroH2A.1-TFAP2C signaling axis that restricts the specification of human germ cell fate.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping