硫氧还原蛋白互作蛋白Txnip在胚胎干细胞中抑制早期胚胎基因表达

Thioredoxin Interacting Protein Txnip Represses Early Embryo Genes in Embryonic Stem Cells

胚胎干细胞是一种具有高发育潜能的多能干细胞.虽然胚胎干细胞中有极少量细胞高表达2细胞早期胚胎相关基因,但是这些2细胞基因却在大部分胚胎干细胞中被沉默.2细胞胚胎相关基因被哪些因子所沉默仍不完全清楚.发现硫氧还原蛋白互作蛋白Txnip是胚胎干细胞中抑制2细胞早期胚胎标志基因如Zscan4与MERVL的关键因素.使用shRNA干扰Txnip的表达或者用CRISPR/Cas9敲除Txnip不影响胚胎干细胞多能性维持却可以激活Zscan4与MERVL等2细胞早期胚胎标志基因的表达.为后续研究Txnip在胚胎干细胞中的作用机制奠定了基础.

Embryonic stem cells are a type of pluripotent stem cell with high developmental potential.A minority of embryonic stem cells highly express genes of the 2-cell embryo during early development.However,these 2-cell genes are silenced in most embryonic stem cells.The silencing factors of these 2-cell genes are still incompletely understood.This study finds that the thioredoxin interacting protein Txnip is a key factor which can repress 2-cell embryo marker genes such as Zscan4 and MERVL in embryonic stem cells.Depletion of Tanip with shRNA or knockout of Tanip with CRISPR/Cas9 does not affect pluripotency but can activate the expression of 2-cell embryo marker genes such as Zscan4 and MERVL.This study has laid the foundation for future studies of the mechanism of Tnip function in embryonic stem cells.