Chemical-induced chromatin remodeling reprograms mouse ESCs to totipotent-like stem cells
Chemical-induced chromatin remodeling reprograms mouse ESCs to totipotent-like stem cells
复制标题
化学诱导的染色质重塑将小鼠 ESC 重新编程为全能样干细胞
DOI：
10.1016/j.stem.2022.01.010
复制
发表时间：
2022-03-03
期刊：
影响因子：
23.9
通讯作者：
Wang, Jichang
中科院分区：
文献类型：
--
作者：
Yang, Mingzhu;Yu, Hanwen;Wang, Jichang
全能细胞比任何其他类型的细胞都具有更强大的发育潜力，从而产生胚胎和胚外组织。稳定的全能性细胞培养和破译全能性调节的原则将是非常宝贵的理解细胞可塑性和谱系分离在早期发展。我们的方法重塑的着丝粒周围异染色质和重新建立全能特异性广泛的H3 K4 me 3结构域促进了多能性全能性的转变。我们的方案建立了小鼠2-细胞（2C）胚胎比任何其他2C样细胞更接近的匹配。这些全能样干细胞（TLSC）在培养中是稳定的，并具有小鼠2C胚胎的独特分子特征。在功能上，TLSC能够进行种系传递，并以高频率产生胚胎和胚外谱系。因此，TLSC代表了用于全能性和胚胎学研究的非常有价值的细胞类型。
Totipotent cells have more robust developmental potency than any other cell types, giving rise to both embryonic and extraembryonic tissues. Stable totipotent cell cultures and deciphering the principles of totipotency regulation would be invaluable to understand cell plasticity and lineage segregation in early development. Our approach of remodeling the pericentromeric heterochromatin and re-establishing the totipotency-specific broad H3K4me3 domains promotes the pluri-to-totipotency transition. Our protocol establishes a closer match of mouse 2-cell (2C) embryos than any other 2C-like cells. These totipotent-like stem cells (TLSCs) are stable in culture and possess unique molecular features of the mouse 2C embryo. Functionally, TLSCs are competent for germline transmission and give rise to both embryonic and extraembryonic lineages at high frequency. Therefore, TLSCs represent a highly valuable cell type for studies of totipotency and embryology.