小柯机器人

美国加州大学旧金山分校Adam R. Abate等研究人员合作通过核酸细胞仪鉴定出星形胶质细胞的调节因子。2023年1月4日，《自然》杂志在线发表了这项成果。

Title: Identification of astrocyte regulators by nucleic acid cytometry

Author: Clark, Iain C., Wheeler, Michael A., Lee, Hong-Gyun, Li, Zhaorong, Sanmarco, Liliana M., Thaploo, Shravan, Polonio, Carolina M., Shin, Seung Won, Scalisi, Giulia, Henry, Amy R., Rone, Joseph M., Giovannoni, Federico, Charabati, Marc, Akl, Camilo Faust, Aleman, Dulce M., Zandee, Stephanie E. J., Prat, Alexandre, Douek, Daniel C., Boritz, Eli A., Quintana, Francisco J., Abate, Adam R.

Issue&Volume: 2023-01-04

Abstract: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS)1. Astrocytes are heterogeneous CNS-resident glial cells that participate in the pathogenesis of MS and its model experimental autoimmune encephalomyelitis (EAE)2,3. However, few unique surface markers are available for the isolation of astrocyte subsets, preventing their analysis and the identification of candidate therapeutic targets; these limitations are further amplified by the rarity of pathogenic astrocytes. To address these challenges, we developed FIND-seq (Focused Interrogation of cells by Nucleic acid Detection and Sequencing), a high-throughput microfluidic cytometry method that combines encapsulation of cells in droplets, PCR-based detection of target nucleic acids, and droplet sorting to enable in-depth transcriptomic analyses of cells of interest at single-cell resolution. We applied FIND-seq to study the regulation of astrocytes characterized by the splicing-driven activation of the transcription factor XBP1, which promotes disease pathology in MS and EAE4. Using FIND-seq in combination with conditional knock-out mice, in vivo CRISPR/Cas9-driven genetic perturbation studies, and bulk and single-cell RNA-seq analyses of mouse EAE and human MS samples, we identified a new role for the nuclear receptor NR3C2 and its corepressor NCOR2 in limiting XBP1-driven pathogenic astrocyte responses. In summary, FIND-seq enabled the identification of a therapeutically targetable mechanism that limits XBP1-driven pathogenic astrocyte responses. FIND-seq allows the investigation of previously inaccessible cells, including rare cell subsets defined by unique gene expression signatures or other nucleic acid markers.

DOI: 10.1038/s41586-022-05613-0

Source: https://www.nature.com/articles/s41586-022-05613-0

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html