Joint epigenome profiling reveals cell-type-specific gene regulatory programmes in human cortical organoids

Research output: Contribution to journalResearch articleContributedpeer-review



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.


Original languageEnglish
Number of pages11
JournalNature cell biology
Issue number12
Publication statusPublished - 23 Nov 2023

External IDs

ORCID /0000-0002-7157-0372/work/147674691
Scopus 85177634151


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