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
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

1873-1883

Subventions

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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Auteurs

Florian Noack (F)

Helmholtz Pioneer Campus, Helmholtz Zentrum München, Neuherberg, Germany.

Silvia Vangelisti (S)

Helmholtz Pioneer Campus, Helmholtz Zentrum München, Neuherberg, Germany.

Nora Ditzer (N)

Center for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden, Germany.

Faye Chong (F)

Helmholtz Pioneer Campus, Helmholtz Zentrum München, Neuherberg, Germany.

Mareike Albert (M)

Center for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden, Germany.

Boyan Bonev (B)

Helmholtz Pioneer Campus, Helmholtz Zentrum München, Neuherberg, Germany. boyan.bonev@helmholtz-munich.de.
Physiological Genomics, Biomedical Center, Ludwig-Maximilians-Universität München, Munich, Germany. boyan.bonev@helmholtz-munich.de.

Classifications MeSH