Chromatin remodeler INO80 mediates trophectoderm permeability barrier to modulate morula-to-blastocyst transition

Abstract

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.

Genetic basis of phenotypic convergence in pig terminal sires using pathway‐based selection signature detection methods

“…A total of 47 candidate regions spanning 4.77 Mb were identified as parallel selection signals between the two populations (Figure S3 and S4). Based on the annotation of functional genes within the potential regions under parallel selection, we found that INO80 and FZR1 associated with reproduction (Cao et al., 2021; Yamamuro et al., 2008), INS , PDE4B and LEPR related to adipose tissue deposition (Bou et al., 2014; Wang et al., 2022; Xu et al., 2022) and FAF1 involved in skeletal development (Rangkasenee et al., 2013) exhibited evidence of parallel selection (Table S5).…”

Overview of junctional complexes during mammalian early embryonic development

“…A study showed that knockdown of AP-2γ (Tcfap2c), a novel upstream regulator of Cdx2 expression, causes downregulation of Pard6b, Tjp2, Cldn4, Cldn6, Cldn7 and prevents TJ formation and paracellular sealing at apical cell borders, inhibiting blastocyst formation ( 60 , 61 ). Knockdown of INO80 in porcine embryos impaired blastocyst development, paracellular sealing of TE, and decreased expression of OCT4, CDX2, TEAD4, CDH1, OCLN and several cell polarity, cytoskeleton and fluid-accumulation related genes ( 62 ).…”

VGLL1 cooperates with TEAD4 to control human trophectoderm lineage specification

“…The placenta mediates exchanges between the maternal uterus and the fetus by supplying nutrients, producing hormones, eliminating waste products, and enabling gas diffusion via maternal blood circulation. In line with these functions, abnormalities in placental development are one of the key reasons for early pregnancy loss and are also responsible for many pregnancy-related diseases including preeclampsia [2][3][4] . Due to ethical considerations and difficulties in obtaining study material, the genetic regulatory mechanisms underlying the formation of human TE and early cytotrophoblast remain unclear.…”