北京大学杜鹏团队近期取得重要工作进展，他们研究提出通过剪接体抑制在人细胞中捕获全能性。相关研究成果2024年6月5日在线发表于《细胞》杂志上。

据介绍，合子的分裂产生全能的卵裂球。在人类8细胞卵裂球中，合子基因组激活（ZGA）启动个体发生程序。然而，在人体细胞中捕获和维持全能性还具有重大挑战。

研究人员实现了培养人全能卵裂球样细胞（hTBLC）。研究人员发现，剪接抑制可以将人类多能干细胞短暂地重新编程为ZGA样细胞（ZLC），在长期传代后，转变为稳定的hTBLC。与已报道的8细胞样细胞（8CLC）不同，ZLC和hTBLC都广泛沉默多能干细胞相关基因。ZLC激活了一组特定的ZGA特异性基因，hTBLC富含ZGA前特异性基因。

在自发分化过程中，hTBLC重新进入中间ZLC阶段，并进一步产生外胚层（EPI）、原始内胚层（PrE）和滋养外胚层（TE）样谱系，有效再现了人类植入前的发育。hTBLC同时具有胚胎和胚胎外发育潜能，可以在体外自主产生类似胚泡的结构，而无需外部细胞信号。

总之，这一研究为人类细胞全能性提供了关键标准和见解。

附：英文原文

Title: Capturing totipotency in human cells through spliceosomal repression

Author: Shiyu Li, Min Yang, Hui Shen, Li Ding, Xuehui Lyu, Kexin Lin, Jennie Ong, Peng Du

Issue&Volume: 2024-06-05

Abstract: The cleavage of zygotes generates totipotent blastomeres. In human 8-cell blastomeres,zygotic genome activation (ZGA) occurs to initiate the ontogenesis program. However,capturing and maintaining totipotency in human cells pose significant challenges.Here, we realize culturing human totipotent blastomere-like cells (hTBLCs). We findthat splicing inhibition can transiently reprogram human pluripotent stem cells intoZGA-like cells (ZLCs), which subsequently transition into stable hTBLCs after long-termpassaging. Distinct from reported 8-cell-like cells (8CLCs), both ZLCs and hTBLCswidely silence pluripotent genes. Interestingly, ZLCs activate a particular groupof ZGA-specific genes, and hTBLCs are enriched with pre-ZGA-specific genes. Duringspontaneous differentiation, hTBLCs re-enter the intermediate ZLC stage and furthergenerate epiblast (EPI)-, primitive endoderm (PrE)-, and trophectoderm (TE)-like lineages,effectively recapitulating human pre-implantation development. Possessing both embryonicand extraembryonic developmental potency, hTBLCs can autonomously generate blastocyst-likestructures in vitro without external cell signaling. In summary, our study provides key criteria andinsights into human cell totipotency.

DOI: 10.1016/j.cell.2024.05.010

Source: https://www.cell.com/cell/abstract/S0092-8674(24)00519-1