Single-cell sequencing insights into the transcriptional landscape of Parkinson's disease

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder, with an unknown etiology and no specific treatment. Emerging single-cell and single-nucleus RNA sequencing (sc/snRNA-seq) technologies have become instrumental in unravelling cellular heterogeneity and characterizing molecular signatures at single-cell resolution. Single-cell T cell receptor sequencing (scTCR-seq) and single-cell B cell receptor sequencing (scBCR-seq) technologies provide unprecedented opportunities to explore the immune repertoire diversity. These state-of-the-art technologies have been increasingly applied in PD research in the last five years, offering novel insights into the cellular susceptibilities and complex molecular mechanisms underlying PD pathogenesis. Herein we review recent advances in the applications of sc/snRNA-seq, scTCR-seq and scBCR-seq technologies in various PD models. Moreover, we focus on degenerative neurons, activated neuroglial cells, as well as pro-inflammatory immune cells, exploring their unique transcriptional landscapes in PD, as revealed by single-cell sequencing technologies. Finally, we highlight important challenges and the future directions of single-cell experiments in PD research.