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

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 two-cell blastomeres prevented its progeny predominantly toward the inner cell mass (ICM) fate, thus indicating that the differential distribution of HSPA2 in the blastomeres of two-cell embryos can influence the selection of embryonic cell lineages. In contrast, the overexpression of Hspa2 in one of the two-cell blastomeres did not induce blastomeres to differentiate towards the ICM fate. Furthermore, we demonstrated that HSPA2 forms a complex with CARM1 and activates ICM-specific gene expression. Collectively, our data identify HSPA2 as a critical regulator of the first cell fate decision which specifies the ICM via the execution of commitment and differentiation phases. To test the heterogeneous distribution of HSPA2 in late 2-cell plays a direct or indirect role in the early stages of lineage commitment., we knocked down the expression of Hspa2 by injecting Hspa2-specific small interfering RNA (siRNA) which targeted the gene in the coding region into the cytoplasm of zygote; NC-FAM (negative control with FAM label) siRNA-injected embryos served as the control