美国加州大学旧金山分校Arnold R. Kriegstein等研究人员合作发现，LIF信号调节人类大脑皮层发育过程中放射状胶质细胞到中间神经元的命运。这一研究成果于2023年9月5日在线发表在国际学术期刊《细胞—干细胞》上。

研究人员表示，放射状胶质细胞（RG）的发育对大脑皮层的生长和组织至关重要。在人类中，外侧放射状胶质细胞（oRG）亚型扩大，并产生多种神经元和胶质细胞。

研究人员发现，oRG细胞在神经发生过程中表达白血病抑制因子（LIF）受体，与干细胞自我更新中的作用一致，LIF扰动会影响大脑皮层组织和器官组织中oRG的增殖。令人惊讶的是，LIF处理还增加了皮层培养物中抑制性中间神经元（IN）的产生。比较转录组分析发现，增强的IN群与尾状神经节突起中产生的IN相似。

为了评估IN是否可能来自于oRG，研究人员分离了原代oRG细胞并用LIF进行培养。研究人员观察到oRG细胞产生了IN，而且LIF处理后IN的丰度有所增加。这些观察结果表明，LIF信号调节了oRG细胞产生IN的能力。

附：英文原文

Title: LIF signaling regulates outer radial glial to interneuron fate during human cortical development

Author: 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

Issue&Volume: 2023-09-05

Abstract: 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.

DOI: 10.1016/j.stem.2023.08.009

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(23)00292-8