Top CUTANA™ CUT&Tag Papers of 2022

2022 saw an impressive number of publications that leveraged CUTANA™ CUT&Tag chromatin mapping technology. Many of these papers merit recognition for advancing epigenetics research, and a complete list can be found on product references page. Below is a brief sampling of publications that stood out for their unique applications of EpiCypher CUT&Tag products and protocols. We hope it provides some inspiration for your own experiments and we look forward to seeing what lies ahead in 2023!

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Tumor microenvironmental signals reshape chromatin landscapes to limit the functional potential of exhausted T cells

Ford et al. Science Immunology, 2022. PMID: 35930654

Cell Types: FACS-sorted tumor-infiltrating CD8+ T cells (exhausted cell states), effector CD8+ T cells from draining lymph nodes (control); all cells from mouse B16F10 melanoma mouse model

Targets: H3K4me3, H3K27me3

Description: T cell exhaustion is an important mechanism associated with cancer immunotherapy resistance. Combating T cell exhaustion requires studying the entire cellular progression from progenitor to terminally differentiated exhausted T cells, including changes to chromatin structure. In this paper, Ford et al. applied ultra-sensitive CUTANA CUT&Tag technology to map open and repressive chromatin during exhausted T cell development. The reduced cell requirements of CUT&Tag enabled high-resolution profiling of multiple histone PTMs from the FACS-sorted cell populations, which revealed distinct chromatin features linked with T cell exhaustion. The authors used these data to identify new epigenetic-based strategies for reactivation of exhausted T cells, pointing to new avenues for immunotherapy-resistant cancer research.

Why it makes the list: This paper underscores the advantages of CUTANA CUT&Tag technologies for profiling rare or small cell populations, including FACS-sorted immune cells.

Characterizing cellular heterogeneity in chromatin state with scCUT&Tag-pro

Zhang et al. Nature Biotechnology, 2022. PMID: 35332340

Cell Types: Frozen PBMCs from healthy human donors

Targets: H3K4me1, H3K4me2, H3K4me3, H3K27ac, H3K27me3, H3K9me3, Phospho-Rpb1 CTD (Ser2/Ser5)

Description: In this paper, Zhang et al. used CUTANA pAG-Tn5 to establish single-cell CUT&Tag-pro (scCUT&Tag-pro), a platform that merges CUT&Tag with detection of cell surface proteins in individual cells. For proof-of-concept, scCUT&Tag-pro was used to profile a collection of histone PTMs in PBMCs. Each experiment mapped one histone PTM per cell with simultaneous detection of common immune cell surface proteins. Individual cells across data sets could be grouped by cell surface markers, and then further separated by chromatin profiling results. These data were combined with publicly available scRNA-seq data to create single-cell “metaomic” profiles.

Why it makes the list: Zhang et al. provide new tools for comprehensive and integrative analysis of chromatin states in heterogeneous cell populations. Their paper also highlights how CUTANA epigenomic technologies can be adapted for user-specific platform development.

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Nuclear RIPK1 promotes chromatin remodeling to mediate inflammatory response

Li et al. Cell Research, 2022. PMID: 35661830

Bonus: Also uses EpiDyne-FRET chromatin remodeling assays!

Cell Types: Mouse embryonic fibroblasts from Ripk1 mutant mice (untreated, TNFα stimulation, TNFα stimulation + RIP1K inhibitor); spinal cord tissue from patients with amyotrophic lateral sclerosis (ALS) and healthy patients

Targets: p-S166-RIPK1 (active RIPK1), SMARCC2, BRG1/SMARCA4, H3K4me1, H3K27ac

Description: Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) modulates cell responses to TNFα cytokine signaling and is linked to increased expression of inflammatory genes in neurodegenerative disease. Although several RIPK1 inhibitors have progressed to clinical trials, the mechanism connecting RIPK1 to transcriptional changes is still unclear. In this paper, Li et al. find that RIPK1 regulates SWI/SNF BAF chromatin remodeling activity at inflammatory genes, increasing chromatin accessibility and promoting gene expression. CUTANA CUT&Tag assays provided key data from cell lines, mouse models, and ALS patient samples, confirming co-localization of RIPK1 and SWI/SNF enzymes at TNFα-induced genes.

Why it makes the list: Understanding how external cues, such as cytokines, are linked to chromatin regulation is important to the identification of new drug targets and more effective treatments.

Epigenetic reader SP140 loss of function drives Crohn’s disease due to uncontrolled macrophage topoisomerases

Amatullah et al. Cell, 2022. PMID: 35952671

Cell Types: Primary human macrophages (control and with siRNA-mediated SP140 knockdown)

Targets: TOP1, TOP2A

Description: Genome-wide association studies (GWAS) for immune diseases have identified multiple risk variants associated with chromatin. Here, Amatullah et al. investigate the function of SP140, an epigenetic reader protein with variants in Crohn’s disease, chronic lymphocytic leukemia, and multiple sclerosis. Using a series of mass spectrometry, cell culture, and CUTANA CUT&Tag experiments, the authors demonstrate that SP140 suppresses topoisomerase activity in healthy cells. GWAS variants of SP140 lead to changes in chromatin accessibility, activation of developmental genes, and defective antimicrobial responses. Treatment of inflammatory bowel disease (IBD) models with topoisomerase inhibitors improved phenotypes specifically in SP140 mutant mice, supporting further exploration for personalized medicine applications.

Why it makes the list: This study illustrates how genome-wide association study (GWAS) variants can interact with chromatin structure to modulate immune cell function and disease. It also underscores the potential of using risk variants to inform treatment strategies.

For a full list of papers citing CUTANA CUT&Tag products see this page.

Thumbnail photo credit: Louis Reed on Unsplash.