LIF信号传导在人类皮质发育过程中调节了外放射状胶质细胞向内神经元分化的命运。
LIF signaling regulates outer radial glial to interneuron fate during human cortical development.
发表日期：2023 Aug 29
作者：
Madeline G Andrews, Clara Siebert, Li Wang, Matthew L White, Jayden Ross, Raul Morales, Megan Donnay, Gradi Bamfonga, Tanzila Mukhtar, Arpana Arjun McKinney, Kaila Gemenes, Shaohui Wang, Qiuli Bi, Elizabeth E Crouch, Neelroop Parikshak, Georgia Panagiotakos, Eric Huang, Aparna Bhaduri, Arnold R Kriegstein
来源：
Cell Stem Cell
摘要：
放射状胶质细胞（RG）的发育对于大脑皮层的生长和组织结构至关重要。在人类中，外层放射状胶质细胞（oRG）亚型扩展并产生多样化的神经元和胶质细胞。然而，调节oRG分化的机制尚不清楚。oRG细胞在神经发生过程中表达白血病抑制因子（LIF）受体，并且与干细胞自我更新的作用一致，LIF干扰影响了皮层组织和器官样体中的oRG增殖。令人惊讶的是，LIF处理还增加了皮层培养中抑制性内源神经元（INs）的产生。比较转录组分析发现，增强的IN人群类似于在尾侧节的成熟中产生的INs。为了评估INs是否可以起源于oRGs，我们分离了初级oRG细胞并将其与LIF一起培养。我们观察到从oRG细胞产生了INs，并且LIF处理后IN的数量增加。我们的观察结果表明，LIF信号调节oRG细胞产生INs的能力。Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Radial glial (RG) development is essential for cerebral cortex growth and organization. In humans, the outer radial glia (oRG) subtype is expanded and gives rise to diverse neurons and glia. However, the mechanisms regulating oRG differentiation are unclear. oRG cells express leukemia-inhibitory factor (LIF) receptors during neurogenesis, and consistent with a role in stem cell self-renewal, LIF perturbation impacts oRG proliferation in cortical tissue and organoids. Surprisingly, LIF treatment also increases the production of inhibitory interneurons (INs) in cortical cultures. Comparative transcriptomic analysis identifies that the enhanced IN population resembles INs produced in the caudal ganglionic eminence. To evaluate whether INs could arise from oRGs, we isolated primary oRG cells and cultured them with LIF. We observed the production of INs from oRG cells and an increase in IN abundance following LIF treatment. Our observations suggest that LIF signaling regulates the capacity of oRG cells to generate INs.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.