近日，奥地利科学院 Jürgen A. Knoblich和 Nina S. Corsini共同合作取得重要进展，他们研究发现人类神经元祖细胞的扩增促进了脑瘤和神经系统的缺陷。该项研究成果于
在这里，研究人员表明人类特定的发育过程是导致皮质发育畸形(MCDs)的原因，这会导致儿童发育迟缓和癫痫。他们建立了结节硬化症(tuberous sclerosis complex, TSC)的人脑类器官模型，并鉴定了一种特定的神经干细胞类型，即尾部晚期中间神经元祖细胞 (caudal late interneuron progenitor，CLIP)。在TSC中，CLIP细胞过度增殖，产生过多的中间神经元、脑肿瘤和皮层畸形。
表皮生长因子受体抑制可减少肿瘤负担，为TSC和相关疾病识别提供了潜在的治疗选择。CLIP细胞的鉴定揭示了人类大脑中延长的中间神经元的产生会导致疾病的易感性。此外，这项工作表明，分析MCDs可以揭示出人类大脑发育特定方面的基本见解。
据悉，人类大脑的进化发育以大脑各个脑区的扩展为特征。
附：英文原文
Title: Amplification of human interneuron progenitors promotes brain tumors and neurological defects
Author: Oliver L. Eichmüller, Nina S. Corsini, ábel Vértesy, Ilaria Morassut, Theresa Scholl, Victoria-Elisabeth Gruber, Angela M. Peer, Julia Chu, Maria Novatchkova, Johannes A. Hainfellner, Mercedes F. Paredes, Martha Feucht, Jürgen A. Knoblich
Issue&Volume: 2022-01-28
Abstract: Evolutionary development of the human brain is characterized by the expansion of various brain regions. Here, we show that developmental processes specific to humans are responsible for malformations of cortical development (MCDs), which result in developmental delay and epilepsy in children. We generated a human cerebral organoid model for tuberous sclerosis complex (TSC) and identified a specific neural stem cell type, caudal late interneuron progenitor (CLIP) cells. In TSC, CLIP cells over-proliferate, generating excessive interneurons, brain tumors, and cortical malformations. Epidermal growth factor receptor inhibition reduces tumor burden, identifying potential treatment options for TSC and related disorders. The identification of CLIP cells reveals the extended interneuron generation in the human brain as a vulnerability for disease. In addition, this work demonstrates that analyzing MCDs can reveal fundamental insights into human-specific aspects of brain development.
DOI: abf5546
Source: https://www.science.org/doi/10.1126/science.abf5546