小柯机器人

美国哈佛医学院Sergiy Velychko等研究人员合作发现，高度协同的嵌合超级SOX诱导跨物种的初始多能性。相关论文于2023年12月22日在线发表于国际学术期刊《细胞—干细胞》。

通过交换Sox2和Sox17之间的结构元件，研究人员构建了一种嵌合超级Sox因子Sox2-17，它能增强小鼠、人类、猴、牛和猪这五种受测物种的iPSC生成。将Sox2和Oct4之间界面上的丙氨酸换成缬氨酸，可通过稳定DNA上的Sox2/Oct4二聚体实现功能增益，从而生成高质量的OSKM iPSC，并支持健康的全iPSC小鼠的发育。

Sox2/Oct4二聚化是初始多能性的核心驱动力，其水平在启动时会降低。瞬时过表达SK鸡尾酒（Sox+Klf4）可恢复二聚化，提高多能干细胞在不同物种中的发育潜能，并为哺乳动物的初始重置提供了一种通用方法。

据介绍，人们对多能性的了解仍然有限：iPSC的生成只在少数模式物种中得到证实，多能干细胞系表现出不一致的发育潜能，种系传递只在小鼠和大鼠中得到证实。

附：英文原文

Title: Highly cooperative chimeric super-SOX induces naive pluripotency across species

Author: Caitlin M. MacCarthy, Guangming Wu, Vikas Malik, Yotam Menuchin-Lasowski, Taras Velychko, Gal Keshet, Rui Fan, Ivan Bedzhov, George M. Church, Ralf Jauch, Vlad Cojocaru, Hans R. Schler, Sergiy Velychko

Issue&Volume: 2023-12-22

Abstract: Our understanding of pluripotency remains limited: iPSC generation has only been established for a few model species, pluripotent stem cell lines exhibit inconsistent developmental potential, and germline transmission has only been demonstrated for mice and rats. By swapping structural elements between Sox2 and Sox17, we built a chimeric super-SOX factor, Sox2-17, that enhanced iPSC generation in five tested species: mouse, human, cynomolgus monkey, cow, and pig. A swap of alanine to valine at the interface between Sox2 and Oct4 delivered a gain of function by stabilizing Sox2/Oct4 dimerization on DNA, enabling generation of high-quality OSKM iPSCs capable of supporting the development of healthy all-iPSC mice. Sox2/Oct4 dimerization emerged as the core driver of naive pluripotency with its levels diminished upon priming. Transient overexpression of the SK cocktail (Sox+Klf4) restored the dimerization and boosted the developmental potential of pluripotent stem cells across species, providing a universal method for naive reset in mammals.

DOI: 10.1016/j.stem.2023.11.010

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(23)00402-2

Cell Stem Cell：《细胞—干细胞》，创刊于2007年。隶属于细胞出版社，最新IF：25.269
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