Single-Cell Sequencing in Neurodegenerative Disorders

Abstract

Neurodegenerative disorders are typically characterized by late onset progressive damage to specific (sub)populations of cells of the nervous system that are essential for mobility, coordination, strength, sensation, and cognition. Addressing this selective cellular vulnerability has become feasible with the emergence of single-cell-omics technologies, which now represent the state-of-the-art approach to profile heterogeneity of complex tissues including human post-mortem brain at unprecedented resolution. In this review, we briefly recapitulate the experimental workflow of single-cell RNA sequencing and summarize the recent knowledge acquired with it in the most common neurodegenerative diseases: Parkinson's, Alzheimer's, Huntington's disease, and multiple sclerosis. We also discuss the possibility of applying single-cell approaches in the diagnostics and therapy of neurodegenerative disorders, as well as the limitations. While we are currently at the point of deeply exploring the transcriptomic changes in the affected cells, further technological developments hold a promise of manipulating the affected pathways once we understand them better.

Fig. 1

Affected brain regions in the most common common neurodegenerative disorders, along with significant publications on sc/snRNA-seq

Fig. 2

Workflow of the scRNA-seq, including a tissue acquisition and b isolation of single cells/nuclei, c barcoding and cell lysis, d RNA isolation and reverse transcription, e sequencing, f data analysis, and g visualization of results

Fig. 3

Major findings in the most common neurodegenerative disorders from sc/snRNA-seq studies, including a Parkinson’s disease, b Alzheimer’s disease, c Huntington’s disease, and d multiple sclerosis