Small intestine and colon tissue-resident memory CD8<sup>+</sup> T cells exhibit molecular heterogeneity and differential dependence on Eomes.
Yun Hsuan Lin, Han G Duong, Abigail E Limary, Eleanor S Kim, Paul Hsu, Shefali A Patel, William H Wong, Cynthia S Indralingam, Yi Chia Liu, Priscilla Yao, Natalie R Chiang, Sara A Vandenburgh, Taylor R Anderson, Jocelyn G Olvera, Amir Ferry, Kennidy K Takehara, Wenhao Jin, Matthew S Tsai, Gene W Yeo, Ananda W Goldrath, John T Chang
Immunity · 2023 · Vol. 56 (1) · pp. 207-223.e8
Abstract
Tissue-resident memory CD8<sup>+</sup> T (T<sub>RM</sub>) cells are a subset of memory T cells that play a critical role in limiting early pathogen spread and controlling infection. T<sub>RM</sub> cells exhibit differences across tissues, but their potential heterogeneity among distinct anatomic compartments within the small intestine and colon has not been well recognized. Here, by analyzing T<sub>RM</sub> cells from the lamina propria and epithelial compartments of the small intestine and colon, we showed that intestinal T<sub>RM</sub> cells exhibited distinctive patterns of cytokine and granzyme expression along with substantial transcriptional, epigenetic, and functional heterogeneity. The T-box transcription factor Eomes, which represses T<sub>RM</sub> cell formation in some tissues, exhibited unexpected context-specific regulatory roles in supporting the maintenance of established T<sub>RM</sub> cells in the small intestine, but not in the colon. Taken together, these data provide previously unappreciated insights into the heterogeneity and differential requirements for the formation vs. maintenance of intestinal T<sub>RM</sub> cells.
Linked datasets 3
Small intestine and colon tissue-resident memory CD8+ T cells exhibit transcriptional, epigenetic, and functional heterogeneity in concert with differential dependence on Eomesodermin [scATAC-seq]
Mus musculus
9 data files
| File | Type | Size |
|---|---|---|
| 1_CIEL_S1_L001_R1_001.fastq.gz | ATAC-seq | 19.4 GB |
| 2_CLPL_S2_L001_R1_001.fastq.gz | ATAC-seq | 16.5 GB |
| 4_SI_IEL_S4_L001_R1_001.fastq.gz | ATAC-seq | 22.1 GB |
| 6_SI_LPL_S6_L001_R1_001.fastq.gz | ATAC-seq | 12.8 GB |
| SRR19560827_GSM6214536 | ATAC-seq | 12.8 GB |
| SRR19560828_GSM6214535 | ATAC-seq | 22.1 GB |
| SRR19560828.lite | ATAC-seq | 22.1 GB |
| SRR19560829_GSM6214534 | ATAC-seq | 16.5 GB |
| SRR19560830_GSM6214533 | ATAC-seq | 19.4 GB |
Small intestine and colon tissue-resident memory CD8+ T cells exhibit transcriptional, epigenetic, and functional heterogeneity in concert with differential dependence on Eomesodermin [CITE-seq]
Mus musculus
32 data files
| File | Type | Size |
|---|---|---|
| 3_19_NE_CIEL_CD45_1_2_ADT_S68_L002_R1_001.fastq.gz | OTHER | 415.0 MB |
| 3_19_NE_CIEL_CD45_1_2_RNA_S68_L003_R1_001.fastq.gz | OTHER | 2.7 GB |
| 3_19_NE_CIEL_CD45_1_ADT_S67_L002_R1_001.fastq.gz | OTHER | 653.8 MB |
| 3_19_NE_CIEL_CD45_1_RNA_S67_L003_R1_001.fastq.gz | OTHER | 4.2 GB |
| 3_19_NE_CLPL_CD45_1_2_ADT_S66_L002_R1_001.fastq.gz | OTHER | 1.5 GB |
| 3_19_NE_CLPL_CD45_1_2_RNA_S66_L003_R1_001.fastq.gz | OTHER | 4.4 GB |
| 3_19_NE_CLPL_CD45_1_ADT_S65_L002_R1_001.fastq.gz | OTHER | 336.6 MB |
| 3_19_NE_CLPL_CD45_1_RNA_S65_L003_R1_001.fastq.gz | OTHER | 3.0 GB |
| 3_19_NE_SIIEL_CD45_1_2_ADT_S62_L002_R1_001.fastq.gz | OTHER | 3.9 GB |
| 3_19_NE_SIIEL_CD45_1_2_RNA_S62_L003_R1_001.fastq.gz | OTHER | 4.8 GB |
| 3_19_NE_SIIEL_CD45_1_ADT_S61_L002_R1_001.fastq.gz | OTHER | 5.2 GB |
| 3_19_NE_SIIEL_CD45_1_RNA_S61_L003_R1_001.fastq.gz | OTHER | 5.4 GB |
| 3_19_NE_SILPL_CD45_1_2_ADT_S64_L002_R1_001.fastq.gz | OTHER | 715.3 MB |
| 3_19_NE_SILPL_CD45_1_2_RNA_S64_L003_R1_001.fastq.gz | OTHER | 2.2 GB |
| 3_19_NE_SILPL_CD45_1_ADT_S63_L002_R1_001.fastq.gz | OTHER | 3.0 GB |
| 3_19_NE_SILPL_CD45_1_RNA_S63_L003_R1_001.fastq.gz | OTHER | 3.9 GB |
| SRR19632528_GSM6235888 | OTHER | 336.0 MB |
| SRR19632529_GSM6235887 | OTHER | 4.4 GB |
| SRR19632530_GSM6235886 | OTHER | 1.5 GB |
| SRR19632531_GSM6235885 | OTHER | 3.0 GB |
| SRR19632532_GSM6235884 | OTHER | 414.0 MB |
| SRR19632533_GSM6235883 | OTHER | 2.7 GB |
| SRR19632534_GSM6235882 | OTHER | 653.0 MB |
| SRR19632535_GSM6235881 | OTHER | 4.2 GB |
| SRR19632536_GSM6235880 | OTHER | 715.0 MB |
| SRR19632537_GSM6235879 | OTHER | 2.2 GB |
| SRR19632538_GSM6235878 | OTHER | 3.0 GB |
| SRR19632539_GSM6235877 | OTHER | 3.9 GB |
| SRR19632540_GSM6235876 | OTHER | 3.9 GB |
| SRR19632541_GSM6235875 | OTHER | 4.8 GB |
| SRR19632542_GSM6235874 | OTHER | 5.2 GB |
| SRR19632543_GSM6235873 | OTHER | 5.4 GB |
Potentially related datasets 2
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.
| Accession | Source | Title |
|---|---|---|
| E-MTAB-9532 | E-MTAB · ArrayExpress | No title in the index |
| GSE205942 | GSE · GEO GEO ↗ | Small intestine and colon tissue-resident memory CD8+ T cells exhibit transcriptional, epigenetic, and functional heterogeneity in concert with differential dependence … |
Analysis pipelines 3
| Pipeline | Assay | Steps | Dataset |
|---|---|---|---|
| GSE205549 scRNA-seq Data Processing geo_data_processing | scRNA-seq | 3 | GSE205549 |
| GSE205941 scRNA-seq Data Processing geo_data_processing | scRNA-seq | 5 | GSE205941 |
| GSE205942 scRNA-seq Data Processing geo_data_processing | scRNA-seq | 3 | GSE205942 |
Funding 11 grants
| Grant | Funder |
|---|---|
| S10 OD026929 | NIH HHS (United States) |
| R01 HG004659 | NHGRI NIH HHS (United States) |
| P30 CA023100 | NCI NIH HHS (United States) |
| P30 DK120515 | NIDDK NIH HHS (United States) |
| R01 AI129973 | NIAID NIH HHS (United States) |
| P01 AI132122 | NIAID NIH HHS (United States) |
| I01 CX002396 | CSRD VA (United States) |
| R01 AI123202 | NIAID NIH HHS (United States) |
| I01 BX005106 | BLRD VA (United States) |
| T32 AR064194 | NIAMS NIH HHS (United States) |
| T32 DK007202 | NIDDK NIH HHS (United States) |