Deciphering Brain Complexity using Single-Cell Sequencing

Abstract

The human brain contains billions of highly differentiated and interconnected cells that form intricate neural networks and collectively control the physical activities and high-level cognitive functions, such as memory, decision-making, and social behavior. Big data is required to decipher the complexity of cell types, as well as connectivity and functions of the brain. The newly developed single-cell sequencing technology, which provides a comprehensive landscape of brain cell type diversity by profiling the transcriptome, genome, and/or epigenome of individual cells, has contributed substantially to revealing the complexity and dynamics of the brain and providing new insights into brain development and brain-related disorders. In this review, we first introduce the progresses in both experimental and computational methods of single-cell sequencing technology. Applications of single-cell sequencing-based technologies in brain research, including cell type classification, brain development, and brain disease mechanisms, are then elucidated by representative studies. Lastly, we provided our perspectives into the challenges and future developments in the field of single-cell sequencing. In summary, this mini review aims to provide an overview of how big data generated from single-cell sequencing have empowered the advancements in neuroscience and shed light on the complex problems in understanding brain functions and diseases.

Transcriptomic signatures of brain regional vulnerability to Parkinson’s disease

“…This would allow us to assess which celltypes might influence regional vulnerability and which genes or modules relate to these cell-type specific processes. Currently, there are many single cell datasets available, but they mainly cover limbic and cortical regions 43,44 , which only includes regions involved in the clinical stages of PD. For the substantia nigra, the hallmark region of PD, there is currently only one human single cell dataset available derived from archived samples 45 .…”

Single-cell transcriptomes of developing and adult olfactory receptor neurons inDrosophila

“…Single-cell RNA sequencing (scRNA-seq) is a powerful tool to investigate the mechanisms underlying nervous system development and function (Ofengeim et al, 2017;Mu et al, 2019;Li, 2020). Recent scRNA-seq studies in the Drosophila nervous system have enabled the discovery of new cell types, mechanisms important for development and aging, and genes controlling neural specification and wiring (Li et al, 2017;Croset et al, 2018;Davie et al, 2018;Avalos et al, 2019;Allen et al, 2020).…”

Transcriptomic analysis of the signature of neurogenesis in human hippocampus suggests restricted progenitor cell progression post-childhood

“…Future studies to answer the question of whether AHN is a significant event will benefit from the combined use of immunohistological and single-cell RNA sequencing (scRNA-seq) techniques to assess lineage-specific expression of neurogenesis markers and to delineate their expression trajectories across developmental stages ( Artegiani et al, 2017 ; Mu et al, 2019 ).…”