PT  - JOURNAL ARTICLE
AU  - Damon Polioudakis
AU  - Luis de la Torre-Ubieta
AU  - Justin Langerman
AU  - Andrew G. Elkins
AU  - Jason L. Stein
AU  - Celine K. Vuong
AU  - Carli K. Opland
AU  - Daning Lu
AU  - William Connell
AU  - Elizabeth K. Ruzzo
AU  - Jennifer K. Lowe
AU  - Tarik Hadzic
AU  - Flora I. Hinz
AU  - Shan Sabri
AU  - William E. Lowry
AU  - Kathrin Plath
AU  - Daniel H. Geschwind
TI  - A single cell transcriptomic analysis of human neocortical development
AID  - 10.1101/401885
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 401885
4099  - http://biorxiv.org/content/early/2018/08/28/401885.short
4100  - http://biorxiv.org/content/early/2018/08/28/401885.full
AB  - Defining the number, proportion, or lineage of distinct cell types in the developing human brain is an important goal of modern brain research. We defined single cell transcriptomic profiles for 40,000 cells at mid-gestation to identify cell types in the developing human neocortex. We define expression profiles corresponding to all known major cell types at this developmental period and identify multiple transcription factors and co-factors expressed in specific cell types, providing an unprecedented resource for understanding human neocortical development including the first single-cell characterization of human subplate neurons. We characterize major developmental trajectories during early neurogenesis, showing that cell type differentiation occurs on a continuum that involves transitions that tie cell cycle progression with early cell fate decisions. We use these data to deconvolute regulatory networks and map neuropsychiatric disease genes to specific cell types, implicating dysregulation of specific cell types, as the mechanistic underpinnings of several neurodevelopmental disorders. Together these results provide an extensive catalog of cell types in human neocortex and extend our understanding of early cortical development, human brain evolution and the cellular basis of neuropsychiatric disease.One Sentence Summary Comprehensive single cell transcriptomes in developing human cortex inform models of cell diversity, differentiation and disease risk.