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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Dec 15, 2017 |
| Title |
ATAC-Seq of CD8+ T cell terminal effector and memory precursor subsets during LCMV infection |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Tissue-resident memory CD8+ T cells (Trm) are positioned at common sites of pathogen exposure where they elicit rapid and robust protective immune responses. However, the molecular signals controlling Trm differentiation and homeostasis are not fully understood. Here we show that mouse Trm precursor cells represent a unique CD8+ T cell subset that is distinct from the precursors of circulating memory populations at the levels of gene expression and chromatin accessibility. Exploiting computational and functional RNAi in vivo screens, we identified the transcription factor (TF) Runx3 as a key regulator of Trm differentiation and homeostasis. Runx3 was required to establish Trm populations in diverse tissue environments and supported expression of critical tissue-residency genes while suppressing genes associated with tissue egress and recirculation. Analysis of the accessibility of Runx3 target genes in Trm-precursor cells revealed a distinct regulatory role for Runx3 in controlling Trm differentiation despite relatively widespread and uniform expression among all CD8+ T cell subsets. Further, we show that human and murine tumor-infiltrating lymphocytes (TIL) share a core tissue-residency gene-expression signature with Trm. In a mouse model of adoptive T cell therapy for melanoma, Runx3-deficient CD8+ TIL failed to accumulate in tumors, resulting in greater rates of tumor growth and mortality. Conversely, overexpression of Runx3 enhanced TIL abundance, delayed tumor growth, and prolonged survival. In addition to establishing Runx3 as a central regulator of Trm differentiation, these results provide novel insight into the signals that promote T cell residency in tissues, which could be leveraged to enhance vaccine efficacy or adoptive cell therapy treatments that target cancer.
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| Overall design |
4 samples, 2 replicates each, Day 7 LCMV infection CD8+ T cell subsets
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| Contributor(s) |
Milner JJ, Goldrath AW |
| Citation(s) |
29211713 |
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| Submission date |
Dec 14, 2017 |
| Last update date |
Mar 21, 2019 |
| Contact name |
John Justin Milner |
| E-mail(s) |
[email protected]
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| Organization name |
UCSD
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| Lab |
Goldrath Lab
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| Street address |
9500 Gilman Dr. MC0377
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| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92093 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE107395 |
Runx3 programs CD8+ T cell residency in non-lymphoid tissues and tumours |
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| Relations |
| BioProject |
PRJNA422431 |
| SRA |
SRP126772 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE108092_RAW.tar |
428.9 Mb |
(http)(custom) |
TAR (of BEDGRAPH) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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