Neurological disorders are among the most heterogeneous and complex categories of disease attributable to the complex cellular changes, coupled with an equally complex microenvironment in the brain. It is hard to underline the impact and importance of single-cell technologies (SCTs) such as single-cell RNA sequencing (scRNA-seq), single-nucleus RNA sequencing (snRNA-seq), and single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) in neuroscience. SCTs allow the researchers to unbiasedly profile thousands of individual cells and their molecular states in the normal and diseased brain tissues. SCTs also revealed previously unappreciated transcriptional and epigenetic changes and have illuminated the progression and heterogeneity of the disease comprehensively. This book chapter presents an overview of the technological concepts, protocols of single-cell platforms, and the research applications of single-cell approaches in the study of neurological disorders. This chapter covers model systems, such as postmortem human brains, induced pluripotent stem cell (iPSC)-derived brain organoids, and animal models. It also provides a discussion of findings involving Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, epilepsy, neurodevelopmental disorders, and neuropsychiatric disorders while indicating how a single-cell perspective can provide access to disease-relevant pathways and cell states in the neuropathology that were previously beyond reach. Here we discuss the limitations and challenges, such as sample preparation, data interpretation, and analysis complexities, as challenges of the research category.

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Unraveling Brain Complexity: The Applications of Single-Cell Technologies in Neurological Disorders

  • Ansh Mehta,
  • Shuvomoy Banerjee,
  • Anand K. Tiwari

摘要

Neurological disorders are among the most heterogeneous and complex categories of disease attributable to the complex cellular changes, coupled with an equally complex microenvironment in the brain. It is hard to underline the impact and importance of single-cell technologies (SCTs) such as single-cell RNA sequencing (scRNA-seq), single-nucleus RNA sequencing (snRNA-seq), and single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) in neuroscience. SCTs allow the researchers to unbiasedly profile thousands of individual cells and their molecular states in the normal and diseased brain tissues. SCTs also revealed previously unappreciated transcriptional and epigenetic changes and have illuminated the progression and heterogeneity of the disease comprehensively. This book chapter presents an overview of the technological concepts, protocols of single-cell platforms, and the research applications of single-cell approaches in the study of neurological disorders. This chapter covers model systems, such as postmortem human brains, induced pluripotent stem cell (iPSC)-derived brain organoids, and animal models. It also provides a discussion of findings involving Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, epilepsy, neurodevelopmental disorders, and neuropsychiatric disorders while indicating how a single-cell perspective can provide access to disease-relevant pathways and cell states in the neuropathology that were previously beyond reach. Here we discuss the limitations and challenges, such as sample preparation, data interpretation, and analysis complexities, as challenges of the research category.