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The asymmetric expression of HSPA2 in blastomeres governs the first embryonic cell-fate decision.

Jiayin Gao | Jiawei Wang | Shiyu Liu | Jinzhu Song | Chuanxin Zhang | Boyang Liu | Keliang Wu
eLife | 2025

The first cell-fate decision is the process by which cells of an embryo take on distinct lineage identities for the first time, thus representing the beginning of developmental patterning. Here, we demonstrate that the molecular chaperone heat shock protein A2 (HSPA2), a member of the 70 kDa heat shock protein (HSP70) family, is asymmetrically expressed in the late 2-cell stage of mouse embryos. The knockdown of Hspa2 in one of the 2-cell blastomeres prevented its progeny predominantly towards the inner cell mass (ICM) fate. In contrast, the overexpression of Hspa2 in one of the 2-cell blastomeres did not induce the blastomere to differentiate towards the ICM fate. Furthermore, we demonstrated that HSPA2 interacted with CARM1 and its levels correlated with ICM-associated genes. Collectively, our results identify HSPA2 as a critical early regulator of the first cell-fate decision in mammalian 2-cell embryos.

Pubmed ID: 40063400

Associated grants

  • Agency: National Natural Science Foundation of China,
    Id: 32170817
  • Agency: Fundamental Research Funds for the Central Universities,
    Id: 2023QNTD004
  • Agency: Fundamental Research Funds for the Central Universities,
    Id: 2022JC006
  • Agency: Taishan Scholars Program of Shandong Province,
    Id: tsqn202211373
  • Agency: Innovative research team of high-level local universities in Shanghai,
    Id: SHSMU-ZLCX20210201
  • Agency: Shandong Provincial Natural Science Foundation,
    Id: 2022HWYQ-034
  • Agency: Shandong Provincial Natural Science Foundation,
    Id: ZR2021QC106

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