Tissue-resident memory CD8 T cell diversity is spatiotemporally imprinted.
Abstract
Tissue-resident memory CD8 T (T<sub>RM</sub>) cells provide protection from infection at barrier sites. In the small intestine, T<sub>RM</sub> cells are found in at least two distinct subpopulations: one with higher expression of effector molecules and another with greater memory potential<sup>1</sup>. However, the origins of this diversity remain unknown. Here we proposed that distinct tissue niches drive the phenotypic heterogeneity of T<sub>RM</sub> cells. To test this, we leveraged spatial transcriptomics of human samples, a mouse model of acute systemic viral infection and a newly established strategy for pooled optically encoded gene perturbations to profile the locations, interactions and transcriptomes of pathogen-specific T<sub>RM</sub> cell differentiation at single-transcript resolution. We developed computational approaches to capture cellular locations along three anatomical axes of the small intestine and to visualize the spatiotemporal distribution of cell types and gene expression. Our study reveals that the regionalized signalling of the intestinal architecture supports two distinct T<sub>RM</sub> cell states: differentiated T<sub>RM</sub> cells and progenitor-like T<sub>RM</sub> cells, located in the upper villus and lower villus, respectively. This diversity is mediated by distinct ligand-receptor activities, cytokine gradients and specialized cellular contacts. Blocking TGFβ or CXCL9 and CXCL10 sensing by antigen-specific CD8 T cells revealed a model consistent with anatomically delineated, early fate specification. Ultimately, our framework for the study of tissue immune networks reveals that T cell location and functional state are fundamentally intertwined.
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Linked Datasets (3)
Tissue-resident memory CD8 T Cell Diversity is Spatiotemporally Imprinted
Mus musculus2 data files
| File | Type | Size |
|---|---|---|
| 44_R_S2_L001_I1_001.fastq.gz | OTHER | 4.7 GB |
| 44_R_S2_L002_I1_001.fastq.gz | OTHER | 4.7 GB |
Tissue-resident memory CD8 T Cell Diversity is Spatiotemporally Imprinted
Mus musculusTissue-resident memory CD8 T Cell Diversity is Spatiotemporally Imprinted [snRNA-Seq]
Mus musculus16 data files
| File | Type | Size |
|---|---|---|
| JC_EL_10XNuclei_c_dist_M1_S12_L002_R1_001.fastq.gz | RNA-Seq | 19.8 GB |
| JC_EL_10XNuclei_c_dist_M1_S8_L002_R1_001.fastq.gz | RNA-Seq | 17.6 GB |
| JC_EL_10XNuclei_c_prox_M1_S11_L002_R1_001.fastq.gz | RNA-Seq | 19.6 GB |
| JC_EL_10XNuclei_c_prox_M1_S7_L002_R1_001.fastq.gz | RNA-Seq | 20.6 GB |
| JC_EL_10XNuclei_si_dist_M1_S5_L002_R1_001.fastq.gz | RNA-Seq | 25.3 GB |
| JC_EL_10XNuclei_si_dist_M1_S9_L002_R1_001.fastq.gz | RNA-Seq | 10.7 GB |
| JC_EL_10XNuclei_si_dist_M2_S10_L002_R1_001.fastq.gz | RNA-Seq | 17.3 GB |
| JC_EL_10XNuclei_si_dist_M2_S6_L002_R1_001.fastq.gz | RNA-Seq | 21.2 GB |
| JC_EL_10XNuclei_si_mid_M1_S3_L002_R1_001.fastq.gz | RNA-Seq | 20.3 GB |
| JC_EL_10XNuclei_si_mid_M1_S7_L002_R1_001.fastq.gz | RNA-Seq | 21.6 GB |
| JC_EL_10XNuclei_si_mid_M2_S4_L002_R1_001.fastq.gz | RNA-Seq | 29.3 GB |
| JC_EL_10XNuclei_si_mid_M2_S8_L002_R1_001.fastq.gz | RNA-Seq | 10.2 GB |
| JC_EL_10XNuclei_si_prox_M1_S1_L002_R1_001.fastq.gz | RNA-Seq | 21.1 GB |
| JC_EL_10XNuclei_si_prox_M1_S5_L002_R1_001.fastq.gz | RNA-Seq | 17.1 GB |
| JC_EL_10XNuclei_si_prox_M2_S2_L002_R1_001.fastq.gz | RNA-Seq | 20.4 GB |
| JC_EL_10XNuclei_si_prox_M2_S6_L002_R1_001.fastq.gz | RNA-Seq | 20.9 GB |
Potentially Related Datasets (3)
These accessions were text-mined from the PMC full text. They may be referenced for comparison, cited from other studies, or otherwise mentioned without being primary data for this paper.
Tissue-resident memory CD8 T Cell Diversity is Spatiotemporally Imprinted [snRNA-Seq]