Zou Wenzheng, Lv Yuqing, Zhang Shukui, Li Lin, Sun Ling, Jiao Jianwei
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; Beijing Institute for Stem Cell and Regenerative Medicine, Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China; Affiliated Hospital of Guangdong Medical University & Key Laboratory of Zebrafish Model for Development and Disease of Guangdong Medical University, Zhanjiang 523710, China.
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; Beijing Institute for Stem Cell and Regenerative Medicine, Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China.
Dev Cell. 2024 Jan 8;59(1):64-78.e5. doi: 10.1016/j.devcel.2023.11.021. Epub 2023 Dec 15.
Mammalian neocortex formation follows a stereotypical pattern wherein the self-renew and differentiation of neural stem cells are coordinated with diverse organelle dynamics. However, the role of lysosomes in brain development has long been overlooked. Here, we demonstrate the highly dynamic lysosomal quantities, types, and localizations in developing brain. We observed asymmetric endolysosome inheritance during radial glial cell (RGC) division and the increased autolysosomes within intermediate progenitor cells (IPs) and newborn neurons. Disruption of lysosomal function shortens the S phase of the cell cycle and promotes RGC differentiation. Mechanistically, we revealed a post-transcriptional regulation governing ribosome homeostasis and cell-cycle progression through differential lysosomal activity modulation. In the human forebrain organoid, lysosomal dynamics are conserved; specifically, during the mitosis of outer subventricular zone RGCs (oRGs), lysosomes are inherited by the progeny without basal process. Together, our results identify the critical role of lysosomal dynamics in regulating mouse and human brain development.
哺乳动物新皮层的形成遵循一种固定模式，其中神经干细胞的自我更新和分化与多种细胞器动态相协调。然而，溶酶体在大脑发育中的作用长期以来一直被忽视。在此，我们展示了发育中大脑中溶酶体数量、类型和定位的高度动态变化。我们观察到放射状胶质细胞（RGC）分裂过程中内溶酶体的不对称遗传，以及中间祖细胞（IP）和新生神经元中自噬溶酶体的增加。溶酶体功能的破坏缩短了细胞周期的S期并促进RGC分化。从机制上讲，我们揭示了一种通过差异溶酶体活性调节来控制核糖体稳态和细胞周期进程的转录后调控。在人类前脑类器官中，溶酶体动态是保守的；具体而言，在外侧脑室下区RGC（oRG）的有丝分裂过程中，溶酶体由没有基底突起的子代继承。总之，我们的结果确定了溶酶体动态在调节小鼠和人类大脑发育中的关键作用。
