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Genome-wide analysis of chromatin accessibility in developing thymic Treg cells

UID: 10516

Author(s): Dikiy, Stanislav*, Feng, Yongqiang*, Zhong, Yi*, Rudensky, Alexander Y.* * MSK affiliated

Description
Summary from the GEO: "We analyzed open chromatin regions in thymic Treg cells, their immediate precursors (CD25+ Foxp3-), and mature and semi-mature CD4 single positive cells. We wished to understand which chromatin regions become accessible in response to TCR-stimulation and then Foxp3 expression as Treg cells develop.
Examination of chromatin accessibility in developing CD4SP thymocyte subsets, including Treg cells and immediate precursors."

The study from which the data originates further explains the information above:

"Regulatory T (T reg) cells, a specialized subset of CD4+ T cells, are essential to prevent fatal autoimmunity. Expression of the T reg lineage-defining transcription factor Foxp3, and therefore their differentiation in the thymus, is dependent upon T cell receptor (TCR) and interleukin-2 (IL-2) signaling. Here, we report that the majority of IL-2-producing cells in the thymus are mature CD4 single-positive (CD4SP) thymocytes and that continuous IL-2 production sustained thymic T reg cell generation and control of systemic immune activation. Furthermore, single-cell RNA sequencing analysis of CD4 thymocyte subsets revealed that IL-2 was expressed in self-reactive CD4SP thymocytes, which also contain T reg precursor cells. Thus, our results suggest that the thymic T reg cell pool size is scaled by a key niche factor, IL-2, produced by self-reactive CD4SP thymocytes. This IL-2-dependent scaling of thymic T reg cell generation by overall self-reactivity of a mature post-selection thymic precursor pool may likely ensure adequate control of autoimmunity."
Subject of Study
Mus musculus
Subject(s)
T-Lymphocytes, Regulatory
Thymocytes
Thymus Gland
Thymus Neoplasms
OncoTree Cancer Type(s)
Thymus
Access via GEO

TAR of CNt and SRA sequencing data.
Accession #: GSE134366

Access via SRA

ATAC sequence reads for 8 samples.
Accession #: SRP214837

Access via BioProject

Additional information about overall initiative.
Accession #: PRJNA554863

Access Restrictions
Free to All
Access Instructions
The NCBI Gene Expression Omnibus, SRA, and BioProject databases provide open access to these files.
Associated Publications
Hemmers S, Schizas M, Azizi E, et al. IL-2 production by self-reactive CD4 thymocytes scales regulatory T cell generation in the thymus. Journal of Experimental Medicine. 2019; 216(11):2466-2478.
Data Type
Genomic
Equipment Used
Illumina HiSeq 2500

High throughput sequencing system

Dataset Format(s)
SRA, TAR, CNt
Dataset Size
3.7 Mb TAR (of CNt), 14.1 Gb (SRA)
Data Catalog Record Updated
2023-12-07