Perspectives on defining cell types in the brain

• Published in: Current opinion in neurobiology 2019-06, Vol.56, p.61-68
• Main Authors: Mukamel, Eran A, Ngai, John
• Format: Article
• Language: English
• Subjects: Brain; Epigenomics; Gene Expression Profiling; Neurosciences; Transcriptome
• ISSN: 0959-4388; 1873-6882
• DOI: 10.1016/j.conb.2018.11.007

•Cell types correspond to self-stabilizing regulatory networks that establish and maintain a core phenotypic program.•Single cell molecular profiling of transcriptomes and epigenomes provides comprehensive and unbiased cell type information.•Molecular data must be integrated with each other and with complementary data on cell morphology, location and physiology.•Collaboration among a wide range of specialists will lead to a more mature and data-driven understanding brain cell types. The diversity of brain cell types was one of the earliest observations in modern neuroscience and continues to be one of the central concerns of current neuroscience research. Despite impressive recent progress, including single cell transcriptome and epigenome profiling as well as anatomical methods, we still lack a complete census or taxonomy of brain cell types. We argue this is due partly to the conceptual difficulty in defining a cell type. By considering the biological drivers of cell identity, such as networks of genes and gene regulatory elements, we propose a definition of cell type that emphasizes self-stabilizing regulation. We explore the predictions and hypotheses that arise from this definition. Integration of data from multiple modalities, including molecular profiling of genes and gene products, epigenetic landscape, cellular morphology, connectivity, and physiology, will be essential for a meaningful and broadly useful definition of brain cell types.