瑞士苏黎世大学Sebastian Jessberger和美国威斯康星大学麦迪逊分校Darcie L. Moore研究组合作取得最新进展。他们表明粘连蛋白B1（LB1）表达下降介导海马干细胞活性的衰老依赖性下降。这一研究成果发表在2021年2月24日出版的《细胞-干细胞》上。

他们表明，小鼠海马神经干细胞（NSC）中的核纤层蛋白层LB1随着年龄的增长而下调，而先前与Hutchinson-Gilford早衰综合征（HGPS）牵连的含SUN结构域的蛋白1（SUN1）的蛋白水平却增加了。平衡衰老的NSC中LB1和SUN1的水平可恢复内质网扩散屏障的强度，这与增殖的NSC中衰老因子的分离有关。

衰老NSCs中基于病毒的LB1表达的恢复增强了体外干细胞的活性，并增加了体内祖细胞的增殖和神经发生。因此，他们在这里确定了介导哺乳动物海马体中与衰老相关的神经发生衰退的机制。

据悉，NSC在整个海马齿状回中产生神经元。随着年龄的增长，神经发生水平急剧下降，这与海马记忆功能的下降有关。但是，介导NSC活性与年龄相关变化的细胞内在机制仍然未知。

附：英文原文

Title: Declining lamin B1 expression mediates age-dependent decreases of hippocampal stem cell activity

Author: Muhammad Khadeesh bin Imtiaz, Baptiste N. Jaeger, Sara Bottes, Raquel A.C. Machado, Mojca Vidmar, Darcie L. Moore, Sebastian Jessberger

Issue&Volume: 2021-02-24

Abstract: Neural stem cells (NSCs) generate neurons throughout life in the hippocampal dentategyrus. With advancing age, levels of neurogenesis sharply drop, which has been associatedwith a decline in hippocampal memory function. However, cell-intrinsic mechanismsmediating age-related changes in NSC activity remain largely unknown. Here, we showthat the nuclear lamina protein lamin B1 (LB1) is downregulated with age in mousehippocampal NSCs, whereas protein levels of SUN-domain containing protein 1 (SUN1),previously implicated in Hutchinson-Gilford progeria syndrome (HGPS), increase. Balancingthe levels of LB1 and SUN1 in aged NSCs restores the strength of the endoplasmic reticulumdiffusion barrier that is associated with segregation of aging factors in proliferatingNSCs. Virus-based restoration of LB1 expression in aged NSCs enhances stem cell activityin vitro and increases progenitor cell proliferation and neurogenesis in vivo. Thus, we here identify a mechanism that mediates age-related decline of neurogenesisin the mammalian hippocampus.

DOI: 10.1016/j.stem.2021.01.015

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(21)00015-1