Journal
SCIENCE
Volume 362, Issue 6420, Pages 1264-+Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aat7615
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Funding
- NIMH [U01MH103392, U01MH103365, U01MH103346, U01MH103340, U01MH103339, R21MH109956, R21MH105881, R21MH105853, R21MH103877, R21MH102791, R01MH111721, R01MH110928, R01MH110927]
- Kavli Foundation
- James S. McDonnell Foundation
- Beatriu de Pinos program [BP-DGR 2014]
- Eunice Kennedy Shriver National Institute of Child Health and Human Development [5R24HD000836]
- Simons Foundation (SFARI) [307705]
- Autism Science Foundation [16-009]
- Joint MRC-Wellcome Trust [MR/R006237/1]
- Netherlands Organization for Scientific Research [NWO VICI 435-14-005]
- Netherlands Scientific Organization (NWO) [480-05-003]
- VU University, Amsterdam, Netherlands
- Dutch Brain Foundation
- [R01MH110926]
- [R01MH110921]
- [R01MH110920]
- [R01MH110905]
- [R01MH109715]
- [R01MH109677]
- [R01MH105898]
- [R01MH094714]
- [R01MH109901]
- [P50MH106934]
- [MH089929]
- [MH090047]
- [MH089921]
- MRC [G0700089] Funding Source: UKRI
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To broaden our understanding of human neurodevelopment, we profiled transcriptomic and epigenomic landscapes across brain regions and/or cell types for the entire span of prenatal and postnatal development. Integrative analysis revealed temporal, regional, sex, and cell type-specific dynamics. We observed a global transcriptomic cup-shaped pattern, characterized by a late fetal transition associated with sharply decreased regional differences and changes in cellular composition and maturation, followed by a reversal in childhood-adolescence, and accompanied by epigenomic reorganizations. Analysis of gene coexpression modules revealed relationships with epigenomic regulation and neurodevelopmental processes. Genes with genetic associations to brain-based traits and neuropsychiatric disorders (including MEF2C, SATB2, SOX5, TCF4, and TSHZ3) converged in a small number of modules and distinct cell types, revealing insights into neurodevelopment and the genomic basis of neuropsychiatric risks.
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