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剪接体抑制能够产生小鼠全能干细胞
作者:小柯机器人 发布时间:2021/5/18 15:21:29

北京大学杜鹏研究组发现,剪接体抑制能够产生小鼠全能干细胞。相关论文于2021年5月14日在线发表在《细胞》杂志上。

研究人员发现,小鼠胚胎干细胞(ESC)剪接体抑制能够驱动多能到全能状态的转换。使用剪接抑制剂Pladienolide B,研究人员可以在全能的ESC上实现稳定的体外培养,这在分子水平上与2细胞和4细胞卵裂球(被称为全卵裂卵球样细胞TBLC)相媲美。小鼠嵌合检测与单细胞RNA测序(scRNA-seq)结合表明TBLC具有强大的双向发育能力,可产生多种胚胎和胚外细胞谱系。

在机制上,剪接体抑制导致多能基因的广泛剪接抑制,而几乎不含短内含子的全能基因被有效剪接并转录激活。这项研究提供了一种捕获和维持全能干细胞的方法。

据了解,自建立第一株ESC以来,实现在功能和分子上与体内卵裂球相当的全能细胞体外培养仍具有巨大挑战性。

附:英文原文

Title: Mouse totipotent stem cells captured and maintained through spliceosomal repression

Author: Hui Shen, Min Yang, Shiyu Li, Jing Zhang, Bing Peng, Chunhui Wang, Zai Chang, Jennie Ong, Peng Du

Issue&Volume: 2021-05-14

Abstract: Since establishment of the first embryonic stem cells (ESCs), in vitro culture of totipotent cells functionally and molecularly comparable with in vivo blastomeres with embryonic and extraembryonic developmental potential has been achallenge. Here we report that spliceosomal repression in mouse ESCs drives a pluripotent-to-totipotentstate transition. Using the splicing inhibitor pladienolide B, we achieve stable in vitro culture of totipotent ESCs comparable at molecular levels with 2- and 4-cell blastomeres,which we call totipotent blastomere-like cells (TBLCs). Mouse chimeric assays combinedwith single-cell RNA sequencing (scRNA-seq) demonstrate that TBLCs have a robust bidirectionaldevelopmental capability to generate multiple embryonic and extraembryonic cell lineages.Mechanically, spliceosomal repression causes widespread splicing inhibition of pluripotentgenes, whereas totipotent genes, which contain few short introns, are efficientlyspliced and transcriptionally activated. Our study provides a means for capturingand maintaining totipotent stem cells.

DOI: 10.1016/j.cell.2021.04.020

Source: https://www.cell.com/cell/fulltext/S0092-8674(21)00500-6

 

期刊信息
Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:36.216
官方网址:https://www.cell.com/