The Asymmetric Expression of HSPA2 in Blastomeres Governs the First Embryonic Cell-fate Decision

Overview

Journal Elife

Specialty Biology

Date 2025 Mar 10

PMID 40063400

Authors

Jiayin Gao

Jiawei Wang

Shiyu Liu

Jinzhu Song

Chuanxin Zhang

Boyang Liu

Keliang Wu

Affiliations

Soon will be listed here.

Abstract

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 in one of the 2-cell blastomeres prevented its progeny predominantly towards the inner cell mass (ICM) fate. In contrast, the overexpression of 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.

Citing Articles

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

Gao J, Wang J, Liu S, Song J, Zhang C, Liu B Elife. 2025; 13.

PMID: 40063400 PMC: 11893103. DOI: 10.7554/eLife.100730.

References

Xu R, Li C, Liu X, Gao S . Insights into epigenetic patterns in mammalian early embryos. Protein Cell. 2020; 12(1):7-28. PMC: 7815849. DOI: 10.1007/s13238-020-00757-z. View

Morris S, Guo Y, Zernicka-Goetz M . Developmental plasticity is bound by pluripotency and the Fgf and Wnt signaling pathways. Cell Rep. 2012; 2(4):756-65. PMC: 3607220. DOI: 10.1016/j.celrep.2012.08.029. View

Bonnycastle L, Yu C, Hunt C, Trask B, Clancy K, Weber J . Cloning, sequencing, and mapping of the human chromosome 14 heat shock protein gene (HSPA2). Genomics. 1994; 23(1):85-93. DOI: 10.1006/geno.1994.1462. View

De Jaime-Soguero A, Abreu de Oliveira W, Lluis F . The Pleiotropic Effects of the Canonical Wnt Pathway in Early Development and Pluripotency. Genes (Basel). 2018; 9(2). PMC: 5852589. DOI: 10.3390/genes9020093. View

Wang J, Wang L, Feng G, Wang Y, Li Y, Li X . Asymmetric Expression of LincGET Biases Cell Fate in Two-Cell Mouse Embryos. Cell. 2018; 175(7):1887-1901.e18. DOI: 10.1016/j.cell.2018.11.039. View

Song J, Zhang J, Yuan X, Liu B, Tao W, Zhang C . Functional substitution of zona pellucida with modified sodium hyaluronate gel in human embryos. J Assist Reprod Genet. 2022; 39(11):2669-2676. PMC: 9723041. DOI: 10.1007/s10815-022-02609-7. View

Rossant J, Tam P . Blastocyst lineage formation, early embryonic asymmetries and axis patterning in the mouse. Development. 2009; 136(5):701-13. DOI: 10.1242/dev.017178. View

Garg M, Kanojia D, Saini S, Suri S, Gupta A, Surolia A . Germ cell-specific heat shock protein 70-2 is expressed in cervical carcinoma and is involved in the growth, migration, and invasion of cervical cells. Cancer. 2010; 116(16):3785-96. DOI: 10.1002/cncr.25218. View

Mu J, Zhou Z, Sang Q, Wang L . The physiological and pathological mechanisms of early embryonic development. Fundam Res. 2024; 2(6):859-872. PMC: 11197659. DOI: 10.1016/j.fmre.2022.08.011. View

10.

Hirate Y, Sasaki H . The role of angiomotin phosphorylation in the Hippo pathway during preimplantation mouse development. Tissue Barriers. 2014; 2(1):e28127. PMC: 4022607. DOI: 10.4161/tisb.28127. View

11.

Pawlak M, Scherer C, Chen J, Roshon M, Ruley H . Arginine N-methyltransferase 1 is required for early postimplantation mouse development, but cells deficient in the enzyme are viable. Mol Cell Biol. 2000; 20(13):4859-69. PMC: 85937. DOI: 10.1128/MCB.20.13.4859-4869.2000. View

12.

Piotrowska K, Zernicka-Goetz M . Role for sperm in spatial patterning of the early mouse embryo. Nature. 2001; 409(6819):517-21. DOI: 10.1038/35054069. View

13.

Chambers I, Silva J, Colby D, Nichols J, Nijmeijer B, Robertson M . Nanog safeguards pluripotency and mediates germline development. Nature. 2007; 450(7173):1230-4. DOI: 10.1038/nature06403. View

14.

Wang Y, Zheng X, Cheng R, Han J, Ma X, Xu W . Asymmetric expression of maternal mRNA governs first cell-fate decision. FASEB J. 2021; 35(11):e22006. DOI: 10.1096/fj.202101196R. View

15.

Picelli S, Faridani O, Bjorklund A, Winberg G, Sagasser S, Sandberg R . Full-length RNA-seq from single cells using Smart-seq2. Nat Protoc. 2014; 9(1):171-81. DOI: 10.1038/nprot.2014.006. View

16.

Korotkevich E, Niwayama R, Courtois A, Friese S, Berger N, Buchholz F . The Apical Domain Is Required and Sufficient for the First Lineage Segregation in the Mouse Embryo. Dev Cell. 2017; 40(3):235-247.e7. PMC: 5300053. DOI: 10.1016/j.devcel.2017.01.006. View

17.

Singh A, Hamazaki T, Hankowski K, Terada N . A heterogeneous expression pattern for Nanog in embryonic stem cells. Stem Cells. 2007; 25(10):2534-42. DOI: 10.1634/stemcells.2007-0126. View

18.

Liu B, Zhao H, Wu K, Grosshans J . Temporal Gradients Controlling Embryonic Cell Cycle. Biology (Basel). 2021; 10(6). PMC: 8228447. DOI: 10.3390/biology10060513. View

19.

Nishioka N, Inoue K, Adachi K, Kiyonari H, Ota M, Ralston A . The Hippo signaling pathway components Lats and Yap pattern Tead4 activity to distinguish mouse trophectoderm from inner cell mass. Dev Cell. 2009; 16(3):398-410. DOI: 10.1016/j.devcel.2009.02.003. View

20.

Torres-Padilla M, Parfitt D, Kouzarides T, Zernicka-Goetz M . Histone arginine methylation regulates pluripotency in the early mouse embryo. Nature. 2007; 445(7124):214-8. PMC: 3353120. DOI: 10.1038/nature05458. View