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Human prefrontal cortex gene regulatory dynamics from gestation to adulthood at single-cell resolution

Charles A Herring, Rebecca K Simmons, Saskia Freytag, Daniel Poppe, Joel J D Moffet, Jahnvi Pflueger, Sam Buckberry, Dulce B Vargas-Landin, Olivier Clément, Enrique Goñi Echeverría, Gavin J Sutton, Alba Alvarez-Franco, Rui Hou, Christian Pflueger, Kerrie McDonald, Jose M Polo, Alistair R R Forrest, Anna K Nowak, Irina Voineagu, Luciano Martelotto, Ryan Lister.
Cell. 2022-10-31;185(23):4428-4447.
Abstract
Human brain development is underpinned by cellular and molecular reconfigurations continuing into the third decade of life. To reveal cell dynamics orchestrating neural maturation, we profiled human prefrontal cortex gene expression and chromatin accessibility at single-cell resolution from gestation to adulthood. Integrative analyses define the dynamic trajectories of each cell type, revealing major gene expression reconfiguration at the prenatal-to-postnatal transition in all cell types followed by continuous reconfiguration into adulthood and identifying regulatory networks guiding cellular developmental programs, states, and functions. We uncover links between expression dynamics and developmental milestones, characterize the diverse timing of when cells acquire adult-like states, and identify molecular convergence from distinct developmental origins. We further reveal cellular dynamics and their regulators implicated in neurological disorders. Finally, using this reference, we benchmark cell identities and maturation states in organoid models. Together, this captures the dynamic regulatory landscape of human cortical development.

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Single-nuclei RNA-seq and single-nuclei ATAC-seq data have been deposited at GEO under accession number GEO: GSE168408 and are publicly available as of the date of publication.
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Accompanying interactive browsers for this study are available at http://brain.listerlab.org.
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All data for the Velmeshev et al. study is publicly available through the Sequence Read Archive, accession number PRJNA434002, and all data for Li et al. (2018) is publicly available through http://development.psychencode.org.
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All original code has been deposited at Zenodo and is publicly available as of the date of publication. DOIs are listed in the key resources table.
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Any additional information required to reanalyze the data reported in this work paper is available from the lead contact (RL) upon request.