埃克塞特大学Hideki Masaki课题组取得一项新突破。他们揭示了抑制PRC2可使黑猩猩胚状能幼稚多能干细胞自我更新。2025年2月26日出版的《细胞—干细胞》杂志发表了这项成果。

课题组人员研究了黑猩猩原始PRC的生成。通过重置或重新编程产生的菌落无法繁殖。课题组研究人员发现自我更新是通过抑制Polycomb suppression complex 2 （PRC2）实现的。扩增后的细胞显示出与人类原始PRC和胚胎着床前外胚层的整体转录组接近，并具有一部分多能性转录因子的共同表达。黑猩猩幼稚的PSCs可以向多系能力过渡，也可以分化为滋养外胚层和下胚层，形成三系囊胚。它们为研究多能性和早期胚胎发生提供了较高的灵长类动物比较模型。基因缺失证实了PRC2介导生长停滞。此外，抑制PRC2克服了人类初始PSCs无饲料繁殖的障碍。因此，染色质修饰H3K27me3的过量沉积是初始PSC自我更新的一个意想不到的障碍。

研究人员表示，原始多能干细胞（PSCs）是哺乳动物胚胎中早期外胚层的对应物。母主题和人类原始PRC在自我更新需求和胚胎外谱系效力方面存在差异。

附：英文原文

Title: Inhibition of PRC2 enables self-renewal of blastoid-competent naive pluripotent stem cells from chimpanzee

Author: Tao Huang, Arthur Radley, Ayaka Yanagida, Zhili Ren, Francesca Carlisle, Somayyeh Tahajjodi, Dongwan Kim, Paul O’Neill, James Clarke, Madeline A. Lancaster, Zoe Heckhausen, Jingran Zhuo, Joo Pedro Agostinho de Sousa, Petra Hajkova, Ferdinand von Meyenn, Hiroo Imai, Hiromitsu Nakauchi, Ge Guo, Austin Smith, Hideki Masaki

Issue&Volume: 2025-02-26

Abstract: Naive pluripotent stem cells (PSCs) are counterparts of early epiblast in the mammalian embryo. Mouse and human naive PSCs differ in self-renewal requirements and extraembryonic lineage potency. Here, we investigated the generation of chimpanzee naive PSCs. Colonies generated by resetting or reprogramming failed to propagate. We discovered that self-renewal is enabled by inhibition of Polycomb repressive complex 2 (PRC2). Expanded cells show global transcriptome proximity to human naive PSCs and embryo pre-implantation epiblast, with shared expression of a subset of pluripotency transcription factors. Chimpanzee naive PSCs can transition to multilineage competence or can differentiate into trophectoderm and hypoblast, forming tri-lineage blastoids. They thus provide a higher primate comparative model for studying pluripotency and early embryogenesis. Genetic deletions confirm that PRC2 mediates growth arrest. Further, inhibition of PRC2 overcomes a roadblock to feeder-free propagation of human naive PSCs. Therefore, excess deposition of chromatin modification H3K27me3 is an unexpected barrier to naive PSC self-renewal.

DOI: 10.1016/j.stem.2025.02.002

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(25)00041-4