近日，美国麻省理工学院Manolis Kellis等研究人员合作完成ALS和FTLD中人类运动皮层和前额叶皮层的单细胞分析。该项研究成果于2024年3月22日在线发表在《细胞》杂志上。
研究人员报告了人类原发性运动皮层和背外侧前额叶皮层的高分辨率比较单细胞分子图谱，以及它们在散发性和家族性肌萎缩性脊髓侧索硬化症（ALS）和额颞叶变性（FTLD）中的转录改变。通过整合转录和遗传信息，研究人员确定了皮层5中已知的和以前未确定的脆弱群体，并表明ALS和FTLD引起的运动神经元和纺锤体神经元，具有几乎无法区分的分子特征。
研究人员揭示了影响这些细胞类型的潜在疾病机制，以及非神经元致病驱动因素。最后，研究人员发现，皮层5中神经元的丢失与转录特征而非细胞形态的关系更为密切，并且超出了之前报道的易损细胞类型。
据悉，ALS和FTLD有许多共同的临床、病理和遗传特征，但对它们在脆弱皮层细胞类型中的相关转录改变却缺乏详细的了解。
附：英文原文
Title: Single-cell dissection of the human motor and prefrontal cortices in ALS and FTLD
Author: S. Sebastian Pineda, Hyeseung Lee, Maria J. Ulloa-Navas, Raleigh M. Linville, Francisco J. Garcia, Kyriakitsa Galani, Erica Engelberg-Cook, Monica C. Castanedes, Brent E. Fitzwalter, Luc J. Pregent, Mahammad E. Gardashli, Michael DeTure, Diana V. Vera-Garcia, Andre T.S. Hucke, Bjorn E. Oskarsson, Melissa E. Murray, Dennis W. Dickson, Myriam Heiman, Veronique V. Belzil, Manolis Kellis
Issue&Volume: 2024-03-22
Abstract: Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) sharemany clinical, pathological, and genetic features, but a detailed understanding oftheir associated transcriptional alterations across vulnerable cortical cell typesis lacking. Here, we report a high-resolution, comparative single-cell molecular atlasof the human primary motor and dorsolateral prefrontal cortices and their transcriptionalalterations in sporadic and familial ALS and FTLD. By integrating transcriptionaland genetic information, we identify known and previously unidentified vulnerablepopulations in cortical layer 5 and show that ALS- and FTLD-implicated motor and spindleneurons possess a virtually indistinguishable molecular identity. We implicate potentialdisease mechanisms affecting these cell types as well as non-neuronal drivers of pathogenesis.Finally, we show that neuron loss in cortical layer 5 tracks more closely with transcriptionalidentity rather than cellular morphology and extends beyond previously reported vulnerable cell types.
DOI: 10.1016/j.cell.2024.02.031
Source: https://www.cell.com/cell/abstract/S0092-8674(24)00234-4