| Title: |
Cell-type-specific DNA methylation dynamics in the prenatal and postnatal human cortex |
| Authors: |
Franklin,Alice; Davies,Jonathan P.; Clifton,Nicholas E.; Blake,Georgina E.T.; Bamford,Rosemary; Walker,Emma M.; Chioza,Barry; Frith,Martyn; Baron-Cohen,Simon; Allison,Carrie; Warrier,Varun; Tsompanidis,Alex; Adhya,Deep; Holt,Rosie; Davis,Joanna; Gu,Genie; Zhang,Yira; Okewole,Niran; Al-Rubaie,Omar; Geschwind,Daniel H.; Ghoddousi,Ramin Ali Marandi; Heazell,Alexander E.P.; Mill,Jonathan; Hurles,Matthew E.; Martin,Hilary C.; Mousa,Mahmoud; Rowitch,David H.; Niakan,Kathy K.; Burton,Graham J.; Ghafari,Fateneh; Srivastava,Deepak P.; Dutan-Polit,Lucia; Pavlinek,Adam; Sichlinger,Laura; Nagy,Roland; Lancaster,Madeline A.; Gonzalez-Martinez,Jose; Biron-Shental,Tal; Gabis,Lidia V.; Rutten,Bart; Gülöksüz, Sinan; Lin, Bochao Danae; van Hell, Erika; van Os, Jim; Pasterkamp, Jeroen; Wiersema, Anna; Boks, Marco; Schalkwijk, Winni; APEX Consortium; Youth-GEMs Consortium; Hersenen-Medisch 1; Onderzoeksgroep 9; Brain; Translational Neuroscience; Regenerative Medicine and Stem Cells; TN groep Pasterkamp; Onderzoek; Onderzoeksgroep 2 |
| Publication Year: |
2025 |
| Subject Terms: |
aging; autism; brain; cortex; development; DNA methylation; epigenetics; fetal; neuronal; schizophrenia; Biochemistry; Genetics and Molecular Biology (miscellaneous); Genetics |
| Description: |
The human cortex undergoes extensive epigenetic remodeling during development, although the precise temporal and cell-type-specific dynamics of DNA methylation remain incompletely understood. In this study, we profiled genome-wide DNA methylation across human cortex tissue from donors aged 6 post-conception weeks to 108 years of age. We observed widespread, developmentally regulated changes in DNA methylation, with pronounced shifts occurring during early- and mid-gestation that were distinct from age-associated modifications in the postnatal cortex. Using fluorescence-activated nuclei sorting, we optimized a protocol for the isolation of SATB2-positive neuronal nuclei, enabling the identification of cell-type-specific DNA methylation trajectories in the developing cortex. Developmentally dynamic DNA methylation sites were significantly enriched near genes implicated in autism and schizophrenia, supporting a role for epigenetic dysregulation in neurodevelopmental conditions. Our findings underscore the prenatal period as a critical window of epigenomic plasticity in the brain with important implications for understanding the genetic basis of neurodevelopmental phenotypes. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
2666-979X |
| Relation: |
https://dspace.library.uu.nl/handle/1874/468850 |
| Availability: |
https://dspace.library.uu.nl/handle/1874/468850 |
| Rights: |
info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.D914D0 |
| Database: |
BASE |