Barandun Niculò, Meier Benjamin, Stehli Gautier, Gräbnitz Fabienne, Zangger Nathan, Oxenius Annette
Institute of Microbiology, ETH Zürich, Vladimir-Prelog-Weg 4, 8093 Zürich, Switzerland.
Institute of Microbiology, ETH Zürich, Vladimir-Prelog-Weg 4, 8093 Zürich, Switzerland.
Cell Rep. 2025 Jan 28;44(1):115127. doi: 10.1016/j.celrep.2024.115127. Epub 2025 Jan 6.
How a single, naive T cell can give rise to diverse progenies of effector and memory cells is not completely understood. One way to achieve this is by asymmetric cell division (ACD), characterized by an unequal distribution of cellular cargo, resulting in divergent daughter cells already after the first division-one being more destined to an effector and the other more to a memory fate. Here, we established two methods to analyze the relative distribution of the older "mother" centrosome and the younger "daughter" centrosome during the first cell division of activated CD8 T cells. We show that upon ACD, the mother centrosome is inherited by the effector-like daughter cell in a ninein-dependent mechanism. Ninein deletion abolished this effect and led to impaired differentiation of memory-like daughter cells. These findings suggest that directed centrosome inheritance upon ACD has functional effects on the fate diversification of CD8 T cells.
单个幼稚T细胞如何产生效应细胞和记忆细胞的多种后代尚未完全明确。实现这一点的一种方式是通过不对称细胞分裂(ACD),其特征是细胞物质分布不均,导致在第一次分裂后就产生不同的子细胞——一个更倾向于成为效应细胞,另一个更倾向于成为记忆细胞命运。在这里,我们建立了两种方法来分析活化的CD8 T细胞第一次细胞分裂过程中较老的“母”中心体和较年轻的“子”中心体的相对分布。我们发现,在不对称细胞分裂时,母中心体以一种依赖九蛋白的机制被效应样子细胞继承。九蛋白缺失消除了这种效应,并导致记忆样子细胞的分化受损。这些发现表明,不对称细胞分裂时定向的中心体遗传对CD8 T细胞的命运多样化具有功能影响。