Journal
CELL REPORTS
Volume 17, Issue 12, Pages 3369-3384Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2016.12.001
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Funding
- Howard Hughes Medical Institute
- Gordon and Betty Moore Foundation [GBMF3034]
- Austrian Academy of Sciences
- Austrian Science Fund [I_1281-B19, Z_153_B09]
- European Research Council (ERC)
- Marie Curie post-doctoral fellowship
- Medical Research Council [MC_UP_1201/9]
- MRC [MC_UP_1201/9] Funding Source: UKRI
- Austrian Science Fund (FWF) [Z153] Funding Source: Austrian Science Fund (FWF)
- Austrian Science Fund (FWF) [Z 153] Funding Source: researchfish
- Medical Research Council [MC_UP_1201/9] Funding Source: researchfish
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Organoids derived from human pluripotent stem cells recapitulate the early three-dimensional organization of the human brain, but whether they establish the epigenomic and transcriptional programs essential for brain development is unknown. We compared epigenomic and regulatory features in cerebral organoids and human fetal brain, using genome-wide, base resolution DNA methylome and transcriptome sequencing. Transcriptomic dynamics in organoids faithfully modeled gene expression trajectories in early-to-mid human fetal brains. We found that early non-CG methylation accumulation at super-enhancers in both fetal brain and organoids marks forthcoming transcriptional repression in the fully developed brain. Demethylated regions (74% of 35,627) identified during organoid differentiation overlapped with fetal brain regulatory elements. Interestingly, pericentromeric repeats showed wide-spread demethylation in multiple types of in vitro human neural differentiation models but not in fetal brain. Our study reveals that organoids recapitulate many epigenomic features of mid-fetal human brain and also identified novel non-CG methylation signatures of brain development.
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