Joint epigenome profiling reveals cell-type-specific gene regulatory programmes in human cortical organoids.
Journal
Nature cell biology
ISSN: 1476-4679
Titre abrégé: Nat Cell Biol
Pays: England
ID NLM: 100890575
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
20
09
2022
accepted:
17
10
2023
pubmed:
24
11
2023
medline:
24
11
2023
entrez:
23
11
2023
Statut:
ppublish
Résumé
Gene expression is regulated by multiple epigenetic mechanisms, which are coordinated in development and disease. However, current multiomics methods are frequently limited to one or two modalities at a time, making it challenging to obtain a comprehensive gene regulatory signature. Here, we describe a method-3D genome, RNA, accessibility and methylation sequencing (3DRAM-seq)-that simultaneously interrogates spatial genome organization, chromatin accessibility and DNA methylation genome-wide and at high resolution. We combine 3DRAM-seq with immunoFACS and RNA sequencing in cortical organoids to map the cell-type-specific regulatory landscape of human neural development across multiple epigenetic layers. Finally, we apply a massively parallel reporter assay to profile cell-type-specific enhancer activity in organoids and to functionally assess the role of key transcription factors for human enhancer activation and function. More broadly, 3DRAM-seq can be used to profile the multimodal epigenetic landscape in rare cell types and different tissues.
Identifiants
pubmed: 37996647
doi: 10.1038/s41556-023-01296-5
pii: 10.1038/s41556-023-01296-5
pmc: PMC10709149
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1873-1883Subventions
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : BO 5516/1-1
Organisme : EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)
ID : 101044469
Organisme : EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)
ID : MOSAIC
Informations de copyright
© 2023. The Author(s).
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