Journal
ZOOLOGICAL RESEARCH
Volume 42, Issue 5, Pages 562-+Publisher
SCIENCE PRESS
DOI: 10.24272/j.issn.2095-8137.2021.075
Keywords
INO80; Blastocyst; Trophectoderm; Tight junction; Permeability
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Funding
- Anhui Provincial Natural Science Foundation [1908085MC97, 2008085MC85]
- National Natural Science Foundation of China [31802059, 31902226]
- Hefei Innovation and Entrepreneurship Support Plan for Returnee Scholar [03082009]
- Anhui Provincial Innovation and Entrepreneurship Support Plan for Returnee Scholar [2020LCX015]
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INO80 plays a crucial role in porcine pre-implantation embryonic development by promoting blastocyst formation and regulating lineage allocation. It functions by modulating the expression of key genes involved in tight junction assembly and fluid accumulation during blastocyst development.
Inositol requiring mutant 80 (INO80) is a chromatin remodeler that regulates pluripotency maintenance of embryonic stem cells and reprogramming of somatic cells into pluripotent stem cells. However, the roles and mechanisms of INO80 in porcine pre-implantation embryonic development remain largely unknown. Here, we show that INO80 modulates trophectoderm epithelium permeability to promote porcine blastocyst development. The INO80 protein is highly expressed in the nuclei during morula-to-blastocyst transition. Functional studies revealed that RNA interference (RNAi)-mediated knockdown of INO80 severely blocks blastocyst formation and disrupts lineage allocation between the inner cell mass and trophectoderm. Mechanistically, single-embryo RNA sequencing revealed that INO80 regulates multiple genes, which are important for lineage specification, tight junction assembly, and fluid accumulation. Consistent with the altered expression of key genes required for tight junction assembly, a permeability assay showed that paracellular sealing is defective in the trophectoderm epithelium of INO80 knockdown blastocysts. Importantly, aggregation of 8-cell embryos from the control and INO80 knockdown groups restores blastocyst development and lineage allocation via direct complementation of the defective trophectoderm epithelium. Taken together, these results demonstrate that INO80 promotes blastocyst development by regulating the expression of key genes required for lineage specification, tight junction assembly, and fluid accumulation.
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