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.
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http://dx.doi.org/10.7554/eLife.100730 | DOI Listing |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893103 | PMC |
Nat Rev Mol Cell Biol
March 2025
Program in Cancer Research, Institut Hospital del Mar d'Investigacions Mèdiques, CIBERONC, Barcelona, Spain.
Many different animal developmental and homeostatic processes rely on signalling via the highly conserved Notch pathway. Often Notch signalling has iterative roles during cell specification and differentiation, controlling not only the state of progenitor cells but also the fate and function of their progeny. Its roles continue throughout the lifespan of the organism, regulating normal tissue maintenance, as well as operating in response to damage.
View Article and Find Full Text PDFAdv Sci (Weinh)
March 2025
Laboratory of Cell Fate Control, School of Life Sciences, Westlake University, Hangzhou, 310030, China.
Porcine embryonic stem cells (ESCs) are excellent models for exploring embryogenesis, producing genetically enhanced farm animals, and improving breeding. Various chemicals have been applied to generate porcine ESCs from embryos, which differ from mouse and human ESC derivation. Wnt inhibitors XAV939 or IWR1 are required to isolate and maintain porcine ESCs.
View Article and Find Full Text PDFElife
March 2025
Institute of Women, Children and Reproductive Health, Shandong University, Jinan, China.
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.
View Article and Find Full Text PDFExplor Target Antitumor Ther
January 2025
Department of Medicine, University of British Columbia, Vancouver, BC V5Z 1M9, Canada.
The discovery of oncogenes and tumor suppressor genes led to a better understanding of tumorigenesis, and prompted the development of molecularly targeted therapy. Over the past 30 years, many new drugs, which are primarily aimed at activated oncogenic proteins in signal transduction pathways involved in cell proliferation and survival, have been introduced in the clinic. Despite its rational design, the overall efficacy of targeted therapy has been modest.
View Article and Find Full Text PDFThe first cell fate bifurcation in mammalian development directs cells toward either the trophectoderm (TE) or inner cell mass (ICM) compartments in preimplantation embryos. This decision is regulated by the subcellular localization of a transcriptional co-activator YAP and takes place over several progressively asyn-chronous cleavage divisions. As a result of this asynchrony and variable arrangement of blastomeres, reconstructing the dynamics of the TE/ICM cell specification from fixed embryos is extremely challenging.
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