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

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dc.contributor.authorHerring, C.A.
dc.contributor.authorSimmons, R.K.
dc.contributor.authorFreytag, S.
dc.contributor.authorPoppe, D.
dc.contributor.authorMoffet, J.J.D.
dc.contributor.authorPflueger, J.
dc.contributor.authorBuckberry, S.
dc.contributor.authorVargas-Landin, D.B.
dc.contributor.authorClément, O.
dc.contributor.authorEcheverría, E.G.
dc.contributor.authorSutton, G.J.
dc.contributor.authorAlvarez-Franco, A.
dc.contributor.authorHou, R.
dc.contributor.authorPflueger, C.
dc.contributor.authorMcDonald, K.
dc.contributor.authorPolo, J.M.
dc.contributor.authorForrest, A.R.R.
dc.contributor.authorNowak, A.K.
dc.contributor.authorVoineagu, I.
dc.contributor.authorMartelotto, L.
dc.contributor.authoret al.
dc.date.issued2022
dc.descriptionPublished: October 31, 2022
dc.description.abstractHuman 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.
dc.description.statementofresponsibilityCharles 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
dc.identifier.citationCell, 2022; 185(23):4428-4447.e28
dc.identifier.doi10.1016/j.cell.2022.09.039
dc.identifier.issn0092-8674
dc.identifier.issn1097-4172
dc.identifier.orcidPolo, J.M. [0000-0002-2531-778X]
dc.identifier.orcidMartelotto, L. [0000-0002-9625-1183]
dc.identifier.urihttps://hdl.handle.net/2440/136967
dc.language.isoen
dc.publisherElsevier
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1130168
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1178460
dc.relation.granthttp://purl.org/au-research/grants/arc/LE170100225
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1184421
dc.relation.granthttp://purl.org/au-research/grants/arc/FT170100359
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/RG170137
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1111206
dc.relation.granthttp://purl.org/au-research/grants/arc/FT180100674
dc.rights© 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/).
dc.source.urihttps://doi.org/10.1016/j.cell.2022.09.039
dc.subjectbrain disorders
dc.subjectcerebral organoids
dc.subjectdevelopment
dc.subjectsingle-cell ATAC-seq
dc.subjectsingle-cell RNA-seq
dc.subject.meshPrefrontal Cortex
dc.subject.meshOrganoids
dc.subject.meshChromatin
dc.subject.meshHumans
dc.subject.meshPregnancy
dc.subject.meshAdult
dc.subject.meshFemale
dc.subject.meshGene Regulatory Networks
dc.subject.meshNeurogenesis
dc.subject.meshSingle-Cell Analysis
dc.titleHuman prefrontal cortex gene regulatory dynamics from gestation to adulthood at single-cell resolution
dc.typeJournal article
pubs.publication-statusPublished

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