Department of Translational Brain Research, Central Institute of Mental Health, University of Heidelberg/Medical Faculty Mannheim, Mannheim, Germany.
HITBR Hector Institute for Translational Brain Research gGmbH, Mannheim, Germany.
Sci Adv. 2022 Feb 11;8(6):eabl5792. doi: 10.1126/sciadv.abl5792.
Symmetric and asymmetric cell divisions are conserved strategies for stem cell expansion and the generation of more committed progeny, respectively. Here, we demonstrate that in human neural stem cells (NSCs), lysosomes are asymmetrically inherited during mitosis. We show that lysosomes contain Notch receptors and that Notch activation occurs the acidic lysosome environment. The lysosome asymmetry correlates with the expression of the Notch target gene and the activity of Notch signaling in the daughter cells. Furthermore, an asymmetry of lysosomes and Notch receptors was also observed in a human organoid model of brain development with mitotic figures showing preferential inheritance of lysosomes and Notch receptor in that daughter cell remaining attached to the apical membrane. Thus, this study suggests a previously unknown function of lysosomes as a signaling hub to establish a bias in Notch signaling activity between daughter cells after an asymmetric cell division of human NSCs.
对称和非对称细胞分裂分别是干细胞扩增和产生更多定型后代的保守策略。在这里，我们证明在人类神经干细胞（NSC）中，溶酶体在有丝分裂期间是不对称遗传的。我们表明溶酶体包含 Notch 受体，并且 Notch 激活发生在酸性溶酶体环境中。溶酶体的不对称性与 Notch 靶基因的表达和 Notch 信号在子细胞中的活性相关。此外，在具有有丝分裂图的人类脑发育类器官模型中也观察到溶酶体和 Notch 受体的不对称性，表明在与顶端膜相连的那个子细胞中，溶酶体和 Notch 受体优先遗传。因此，这项研究表明溶酶体作为信号枢纽的一个先前未知的功能，可在人类 NSC 的不对称细胞分裂后在子细胞之间建立 Notch 信号活性的偏向。
