Cerebral Organoids Recapitulate Epigenomic Signatures of the Human Fetal Brain
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...
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| Format: | Article |
| Language: | English |
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Elsevier
2016-12-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124716316722 |
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| author | Chongyuan Luo Madeline A. Lancaster Rosa Castanon Joseph R. Nery Juergen A. Knoblich Joseph R. Ecker |
| author_facet | Chongyuan Luo Madeline A. Lancaster Rosa Castanon Joseph R. Nery Juergen A. Knoblich Joseph R. Ecker |
| author_sort | Chongyuan Luo |
| collection | DOAJ |
| description | 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 widespread 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. |
| first_indexed | 2024-12-20T19:45:35Z |
| format | Article |
| id | doaj.art-10a4e25db763422881dd1a5fe8f19335 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-20T19:45:35Z |
| publishDate | 2016-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-10a4e25db763422881dd1a5fe8f193352022-12-21T19:28:25ZengElsevierCell Reports2211-12472016-12-0117123369338410.1016/j.celrep.2016.12.001Cerebral Organoids Recapitulate Epigenomic Signatures of the Human Fetal BrainChongyuan Luo0Madeline A. Lancaster1Rosa Castanon2Joseph R. Nery3Juergen A. Knoblich4Joseph R. Ecker5Genomic Analysis Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USAInstitute of Molecular Biotechnology of the Austrian Academy of Science (IMBA), Vienna 1030, AustriaGenomic Analysis Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USAGenomic Analysis Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USAInstitute of Molecular Biotechnology of the Austrian Academy of Science (IMBA), Vienna 1030, AustriaGenomic Analysis Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USAOrganoids 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 widespread 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.http://www.sciencedirect.com/science/article/pii/S2211124716316722DNA methylationepigenomeorganoidbrain development3D culture |
| spellingShingle | Chongyuan Luo Madeline A. Lancaster Rosa Castanon Joseph R. Nery Juergen A. Knoblich Joseph R. Ecker Cerebral Organoids Recapitulate Epigenomic Signatures of the Human Fetal Brain Cell Reports DNA methylation epigenome organoid brain development 3D culture |
| title | Cerebral Organoids Recapitulate Epigenomic Signatures of the Human Fetal Brain |
| title_full | Cerebral Organoids Recapitulate Epigenomic Signatures of the Human Fetal Brain |
| title_fullStr | Cerebral Organoids Recapitulate Epigenomic Signatures of the Human Fetal Brain |
| title_full_unstemmed | Cerebral Organoids Recapitulate Epigenomic Signatures of the Human Fetal Brain |
| title_short | Cerebral Organoids Recapitulate Epigenomic Signatures of the Human Fetal Brain |
| title_sort | cerebral organoids recapitulate epigenomic signatures of the human fetal brain |
| topic | DNA methylation epigenome organoid brain development 3D culture |
| url | http://www.sciencedirect.com/science/article/pii/S2211124716316722 |
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