Transcriptomic diversity of cell types across the adult human brain

• Published in: Science (American Association for the Advancement of Science) Vol. 382; no. 6667; p. eadd7046
• Main Authors: Siletti, Kimberly, Hodge, Rebecca, Mossi Albiach, Alejandro, Lee, Ka Wai, Ding, Song-Lin, Hu, Lijuan, Lönnerberg, Peter, Bakken, Trygve, Casper, Tamara, Clark, Michael, Dee, Nick, Gloe, Jessica, Hirschstein, Daniel, Shapovalova, Nadiya V, Keene, C Dirk, Nyhus, Julie, Tung, Herman, Yanny, Anna Marie, Arenas, Ernest, Lein, Ed S, Linnarsson, Sten
• Format: Journal Article
• Language: English
• Published: United States The American Association for the Advancement of Science 13.10.2023
• Subjects: Adult; Astrocytes; Brain; Brain - cytology; Brain - metabolism; Brain stem; Cerebellum; Cerebral cortex; Clusters; Cognition; Cytology; Dopamine receptors; Electrophysiology; Forebrain; Gene Expression Profiling; Gene sequencing; Glial cells; Glial stem cells; Heterogeneity; Hindbrain; Hippocampus; Humans; Hypothalamus; Interneurons; Medicin och hälsovetenskap; Medulla oblongata; Mesencephalon; Neural networks; Neural stem cells; Neurodegenerative diseases; Neuronal-glial interactions; Neurons; Neurons - metabolism; Neuropeptides; Nuclei (cytology); Oligodendrocytes; Origins; Prosencephalon; Single-Cell Gene Expression Analysis; Telencephalon; Thalamus; Transcriptome
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.add7046

The human brain directs complex behaviors, ranging from fine motor skills to abstract intelligence, but the diversity of cell types that support these skills has not been fully described. In this work, we used single-nucleus RNA sequencing to systematically survey cells across the entire adult human brain. We sampled more than three million nuclei from approximately 100 dissections across the forebrain, midbrain, and hindbrain in three postmortem donors. Our analysis identified 461 clusters and 3313 subclusters organized largely according to developmental origins and revealing high diversity in midbrain and hindbrain neurons. Astrocytes and oligodendrocyte-lineage cells also exhibited regional diversity at multiple scales. The transcriptomic census of the entire human brain presented in this work provides a resource for understanding the molecular diversity of the human brain in health and disease.