Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/15931
Human prefrontal cortex gene regulatory dynamics from gestation to adulthood at single-cell resolution.
Herring, Charles A | Simmons, Rebecca K | Freytag, Saskia | Poppe, Daniel | Moffet, Joel J D | Pflueger, Jahnvi | Buckberry, Sam | Vargas-Landin, Dulce B | Clément, Olivier | Echeverría, Enrique Goñi | Sutton, Gavin J | Alvarez-Franco, Alba | Hou, Rui | Pflueger, Christian | McDonald, Kerrie | Polo, Jose M | Forrest, Alistair R R | Nowak, Anna K | Voineagu, Irina | Martelotto, Luciano | Lister, Ryan
Cell. 2022 Nov 10;185(23):4428-4447.e28.
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.
Organoids | Neurogenesis | Pregnancy | Female | Humans | Adult | Chromatin | Prefrontal Cortex | Single-Cell Analysis | Gene Regulatory Networks
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