INTER-INDIVIDUAL VARIATION IN HUMAN CORTICAL CELL TYPE ABUNDANCE AND EXPRESSION

• DOI: 10.1016/j.ibneur.2023.08.1952
• Publication Date: 2023-11-05T02:57:55Z
• Authors: Nelson Johansen; Saroja Somasundaram; Kyle Travaglini; Anna Marie Yanny; Maya Shumyatcher; Tamara Casper; Charles Cobbs; Nick Dee; Richard Ellenbogen; Manuel Ferreira; Jeff Goldy; Junitta Guzman; Ryder Gwinn; Daniel Hirschstein; Nikolas Jorstad; C. Dirk Keene; Andrew Ko; Boaz Levi; Jeffrey Ojemann; Thanh Pham; Nadiya Shapovalova; Daniel Silbergeld; Josef Sulc; Amy Torkelson; Herman Tung; Kimberly Smith; Ed Lein; Trygve Bakken; Rebecca Hodge; Jeremy Miller
• Keywords: Variation (astronomy); Expression (computer science)

AbstractSingle cell transcriptomic studies have identified a conserved set of neocortical cell types from small post-mortem cohorts. We extend these efforts by assessing cell type variation across 75 adult individuals undergoing epilepsy and tumor surgeries. Nearly all nuclei map to one of 125 robust cell types identified in middle temporal gyrus, but with varied abundances and gene expression signatures across donors, particularly in deep layer glutamatergic neurons. A minority of variance is explainable by known factors including donor identity and small contributions from age, sex, ancestry, and disease state. Genomic variation was significantly associated with variable expression of 150-250 genes for most cell types. Thus, human individuals display a highly consistent cellular makeup, but with significant variation reflecting donor characteristics, disease condition, and genetic regulation.One-Sentence SummaryInter-individual variation in human cortex is greatest for deep layer excitatory neurons and largely unexplainable by known factors.