Human body single-cell atlas of three-dimensional genome organization and DNA methylation
TL;DR
Multiomic profiling of 86,689 single nuclei across 16 human tissues revealed that cell types delineated by DNA methylation differ extensively from those defined by 3D genome structure.
Problem / question
While higher-order chromatin structure and DNA methylation are known to be critical for gene regulation, it remains unclear how these epigenomic features vary across the diverse tissues and cell types of the human body.
Methods
The researchers performed multiomic profiling of three-dimensional genome structure and DNA methylation on 86,689 single nuclei sampled from 16 different human tissues.
Key findings
The analysis identified 35 major cell types and 206 cell subtypes based on the multiomic data. The researchers observed extensive changes in both CG and non-CG methylation across these cell types. Crucially, they found extensive discrepancies between cell types defined by DNA methylation and those defined by 3D genome structure.
Why it matters
This single-cell atlas provides a foundational reference for exploring gene regulation in human health and disease, revealing that the specific epigenomic features used to maintain cell identity vary depending on the cell lineage.
Limitations
The provided text does not explicitly mention any methodological limitations, biases, or constraints.
Takeaway
A multiomic atlas of 86,689 single nuclei across 16 tissues demonstrates that DNA methylation and 3D chromatin structure do not perfectly align in defining cell types, suggesting lineage-specific mechanisms for maintaining cell identity.