ArticleJournal of immunology (Baltimore, Md. : 1950)2024
Single-Molecule DNA Methylation Reveals Unique Epigenetic Identity Profiles of T Helper Cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 2 citations in OpenAlex.
- Acute capillary blood DNA methylation responses to swimming exercise in high-performance male and female swimmers.Experimental physiology · 2026Article
- Improved Cas9-targeted nanopore sequencing facilitates ultra-deep analysis of genomic variation.Cell reports methods · 2026Article
- Methodological Comparison of Short-Read and Long-Read Sequencing Methods on Colorectal Cancer Samples.International journal of molecular sciences · 2025Article
- Unmasking Pediatric Asthma: Epigenetic Fingerprints and Markers of Respiratory Infections.International journal of molecular sciences · 2025Review
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Both identity and plasticity of CD4 T helper (Th) cells are regulated in part by epigenetic mechanisms. However, a method that reliably and readily profiles DNA base modifications is still needed to finely study Th cell differentiation. Cytosine methylation in CpG context (5mCpG) and cytosine hydroxymethylation (5hmCpG) are DNA modifications that identify stable cell phenotypes, but their potential to characterize intermediate cell transitions has not yet been evaluated. To assess transition states in Th cells, we developed a method to profile Th cell identity using Cas9-targeted single-molecule nanopore sequencing. Targeting as few as 10 selected genomic loci, we were able to distinguish major in vitro polarized murine T cell subtypes, as well as intermediate phenotypes, by their native DNA 5mCpG patterns. Moreover, by using off-target sequences, we were able to infer transcription factor activities relevant to each cell subtype. Detection of 5mCpG and 5hmCpG was validated on intestinal Th17 cells escaping transforming growth factor β control, using single-molecule adaptive sampling. A total of 21 differentially methylated regions mapping to the 10-gene panel were identified in pathogenic Th17 cells relative to their nonpathogenic counterpart. Hence, our data highlight the potential to exploit native DNA methylation profiling to study physiological and pathological transition states of Th cells.
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Registered trials
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