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

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  (Published version)

Date

2022

Authors

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.

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Advisors

Journal Title

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Volume Title

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Journal article

Citation

Cell, 2022; 185(23):4428-4447.e28

Statement of Responsibility

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

Conference Name

DOI

10.1016/j.cell.2022.09.039

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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Published: October 31, 2022

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© 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

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Grant ID

http://purl.org/au-research/grants/nhmrc/1130168
 http://purl.org/au-research/grants/nhmrc/1178460
 http://purl.org/au-research/grants/arc/LE170100225
 http://purl.org/au-research/grants/nhmrc/1184421
 http://purl.org/au-research/grants/arc/FT170100359
 http://purl.org/au-research/grants/nhmrc/RG170137
 http://purl.org/au-research/grants/nhmrc/1111206
 http://purl.org/au-research/grants/arc/FT180100674

Published Version

https://doi.org/10.1016/j.cell.2022.09.039

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Persistent link to this record

https://hdl.handle.net/2440/136967