부산대학교 도서관

Keywords development; single-cell RNA-seq; single-cell ATAC-seq; brain disorders; cerebral organoids Highlights * Single-nucleus RNA and chromatin dynamics from gestation to adulthood in humans * Protracted and diverse timing of cell-type development to a mature state * RNA dynamics and regulators predict cellular and temporal origins of brain diseases * Atlas integration reveals few postnatal maturity neurons in long-term brain organoids Summary 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. Author Affiliation: (1) Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Perth, WA 6009, Australia (2) ARC Centre of Excellence in Plant Energy Biology, School of Molecular Sciences, The University of Western Australia, Perth, WA 6009, Australia (3) School of Biotechnology and Biomolecular Sciences, Cellular Genomics Futures Institute, and the RNA Institute, University of New South Wales, Sydney, NSW 2052, Australia (4) Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid 28029, Spain (5) Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW 2052, Australia (6) Adelaide Centre for Epigenetics and the South Australian Immunogenomics Cancer Institute, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, SA 5000, Australia (7) Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC 3000, Australia (8) Medical School, University of Western Australia, Perth, WA 6009, Australia (9) University of Melbourne Centre for Cancer Research, Victoria Comprehensive Cancer Centre, Melbourne, VIC 3000, Australia * Corresponding author Article History: Received 29 October 2021; Revised 19 July 2022; Accepted 27 September 2022 (miscellaneous) Published: October 31, 2022 (footnote)10 These authors contributed equally (footnote)11 Lead contact Byline: Charles A. Herring (1,2,10), Rebecca K. Simmons (1,2,10), Saskia Freytag (1,2,10), Daniel Poppe (1,2,10), Joel J.D. Moffet (1), Jahnvi Pflueger (1,2), Sam Buckberry (1,2), Dulce B. Vargas-Landin (1,2), Olivier Clément (1,2), Enrique Goñi Echeverría (1), Gavin J. Sutton (3), Alba Alvarez-Franco (4), Rui Hou (1), Christian Pflueger (1,2), Kerrie McDonald (5), Jose M. Polo (6,7), Alistair R.R. Forrest (1), Anna K. Nowak (8), Irina Voineagu (3), Luciano Martelotto (6,9), Ryan Lister [ryan.lister@uwa.edu.au] (1,2,11,*)