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

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

Abstract

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.

Details

Original languageEnglish
Number of pages11
JournalNature cell biology
Volume25
Issue number12
Publication statusPublished - 23 Nov 2023
Peer-reviewedYes

External IDs

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

Keywords

Sustainable Development Goals