Christopher Hartl, PhD
Manager – Bioinformatics
Epigenome Technologies, San Diego, CA
Talk Title: Deciphering Single-Cell Chromatin Landscapes in the Human Immune System: A First Look
Host: Dr. Ting Wang
Abstract: Cellular identity and gene expression programs are imprinted and maintained by epigenetic mechanisms, but precise mapping of histone-mediated regulatory factors in tissues has been hindered by cell heterogeneity. Recent technological advances in single-cell histone profiling, specifically single-cell Cut&Tag and Paired-Tag methodologies, now enable detailed mapping of chromatin landscapes without prior cell sorting. Utilizing peripheral blood mononuclear cells (PBMCs) from multiple donors, we generated over 70,000 single-cell histone modification profiles (H3K4me1, H3K4me3, H3K27ac, and H3K27me3), accurately reflecting bulk epigenomic signatures and providing a detailed preliminary atlas of chromatin states in circulating human immune cells.
More than 650,000 regions of chromatin modification were identified, grouping into approximately 120,000 candidate cis-regulatory elements (cCREs). Most cCREs exhibited widespread activity across immune populations, defining a core epigenomic signature, while a sizeable subset displayed cell-type specificity indicative of roles in lineage commitment and functional identity. We highlighted regulatory regions demonstrating cell-specific bivalent chromatin signatures marked simultaneously by activating (H3K4me3) and repressive (H3K27me3) modifications, suggesting poised regulatory states with potential for dynamic transcriptional responses.
Chromatin state clustering at transcription factor-binding sites, particularly those bound by interferon regulatory factors (IRFs), revealed distinct activation patterns correlated with immunological function and cell-type-specific responsiveness. These findings illustrate the capability of single-cell histone profiling technologies to dissect immune regulatory networks, offering powerful tools for identifying epigenetic signatures linked to immune function, maturation, and disease pathology.