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Type: Journal article
Title: Human prefrontal cortex gene regulatory dynamics from gestation to adulthood at single-cell resolution
Author: Herring, C.A.
Simmons, R.K.
Freytag, S.
Poppe, D.
Moffet, J.J.D.
Pflueger, J.
Buckberry, S.
Vargas-Landin, D.B.
Clément, O.
Echeverría, E.G.
Sutton, G.J.
Alvarez-Franco, A.
Hou, R.
Pflueger, C.
McDonald, K.
Polo, J.M.
Forrest, A.R.R.
Nowak, A.K.
Voineagu, I.
Martelotto, L.
et al.
Citation: Cell, 2022; 185(23):4428-4447.e28
Publisher: Elsevier
Issue Date: 2022
ISSN: 0092-8674
Statement of
Charles A. Herring, Rebecca K. Simmons, Saskia Freytag, Daniel Poppe, Joel J.D. Moffet, Jahnvi Pflueger, Sam Buckberry, Dulce B. Vargas-Landin, Olivier Cle, ment, Enrique Gon, i Echeverrı, a, 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, and Ryan Lister
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.
Keywords: brain disorders
cerebral organoids
single-cell ATAC-seq
single-cell RNA-seq
Description: Published: October 31, 2022
Rights: © 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (
DOI: 10.1016/j.cell.2022.09.039
Grant ID:
Appears in Collections:Medicine publications
South Australian Immunogenomics Cancer Institute (SAIGENCI) publications

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