Chromatin accessibility landscapes define stromal cell identities across tissues

Area of Science:

• Genomics
• Epigenetics
• Cell Biology

Background:

• Chromatin accessibility is vital for gene regulation and cellular identity.
• Single-cell RNA sequencing advanced transcriptomics, but chromatin dynamics across tissues need further exploration.

Purpose of the Study:

• To create a comprehensive atlas of chromatin accessibility across diverse murine tissues.
• To identify cell types and regulatory elements defining tissue and cell-specific epigenomic landscapes.
• To investigate the potential of chromatin accessibility for tracing cell origins.

Main Methods:

• Single-cell Assay for Transposase-Accessible Chromatin sequencing (scATAC-seq) was performed on 51,248 cells from nine mouse tissues.
• Data analysis involved identifying cell types, characterizing cis-regulatory elements, and performing motif enrichment analyses.
• A metacell approach was utilized to define tissue-specific chromatin modules.

Main Results:

• Identified 28 major cell types with distinct chromatin accessibility signatures across tissues.
• Discovered conserved and tissue-specific cis-regulatory elements and associated transcription factor motifs.
• Demonstrated that chromatin accessibility profiles can trace stromal cells (endothelial cells, fibroblasts, macrophages) to their tissue of origin.
• Revealed specific chromatin modules reflecting tissue-specific epigenomic landscapes.

Conclusions:

• This study provides a valuable atlas of chromatin accessibility in murine tissues, illuminating regulatory architecture.
• Chromatin accessibility signatures are key determinants of cell-type and tissue specificity.
• The ability to trace cell origins via chromatin profiles has significant implications for disease diagnostics and therapeutics.