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 Vargas Landin, Olivier Clement, Enrique Goni Echeverria, 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 MartelottoRyan Lister

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)4428-4447.e28
Number of pages20
JournalCell
Volume185
Issue number23
DOIs
Publication statusPublished - 10 Nov 2022

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