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| Status |
Public on Apr 25, 2016 |
| Title |
Hobit and Blimp1 instruct a universal transcriptional program of tissue-residency in lymphocytes |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Tissue-resident memory T cells (Trm) are non-circulating memory T cells that localize to portals of pathogen entry such as the skin, gut and lung where they provide efficient early protection against reinfection. Trm are characterized by a molecular profile that actively prevents egress from peripheral sites including the constitutive expression of the lectin CD69 and down-regulation of the chemokine receptor (CCR)7 and sphingosine-1-phosphate receptor 1 (S1PR1). This program is partially mediated by down-regulation of the transcription factor KLF2; however, to date no transcriptional regulator specific to Trm has been identified. Here we show that the Blimp1 related transcription factor Hobit is specifically upregulated in Trm and together with Blimp1, mediates the development and maintenance of Trm in various tissues including skin, gut, liver and kidney. Importantly, we found that the Hobit/Blimp1 transcriptional module is also required for other tissue-resident lymphocytes including Natural Killer T (NKT) cells and liver tissue-resident NK cells (trNK). We show that these populations share a universal transcriptional program with Trm instructed by Hobit and Blimp1 that includes the repression of CCR7, S1PR1 and KLF2 thereby enforcing tissue retention. Our results identify Hobit and Blimp1 as major common regulators that drive the differentiation of distinct populations of tissue-resident lymphocytes.
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| Overall design |
RNA-seq data were generated for multiple tissues in mice to investigate global expression difference between resident and circulating cells.
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| Contributor(s) |
Shi W, Liao Y, Kallies A, van Gisbergen K |
| Citation(s) |
27102484 |
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| Submission date |
Jul 13, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Wei Shi |
| E-mail(s) |
Wei.Shi@onjcri.org.au
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| Organization name |
Olivia Newton John Cancer Research Institute
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| Department |
Bioinformatics and Cancer Genomics
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| Street address |
Level 5, ONJ Cancer Centre, 145 Studley Rd
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| City |
Heidelberg |
| State/province |
VIC |
| ZIP/Postal code |
3084 |
| Country |
Australia |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (38)
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| GSM1819904 |
Blimp1/Hobit double knockout rep1 |
| GSM1819905 |
Wild type rep2 |
| GSM1819906 |
Hobit knockout rep2 |
| GSM1819907 |
Blimp1 knockout rep2 |
| GSM1819908 |
Blimp1/Hobit double knockout rep2 |
| GSM1819909 |
Wild type rep3 |
| GSM1819910 |
Hobit knockout rep3 |
| GSM1819911 |
Blimp1 knockout rep3 |
| GSM1819912 |
Blimp1/Hobit double knockout rep3 |
| GSM1819913 |
Naive CD8 T cells, spleen, rep1 |
| GSM1819914 |
LCMV central memory CD8 T cells, spleen, rep1 |
| GSM1819915 |
LCMV effector memory CD8 T cells, spleen, rep1 |
| GSM1819916 |
LCMV effector memory CD8 T cells, liver, rep1 |
| GSM1819917 |
LCMV tissue-resident memory CD8 T cells, liver, rep1 |
| GSM1819918 |
LCMV tissue-resident memory CD8 T cells, gut, rep1 |
| GSM1819919 |
LCMV conventional nature killer cells, liver, rep1 |
| GSM1819920 |
LCMV tissue-resident nature killer cells, liver, rep1 |
| GSM1819921 |
LCMV nature killer T cells, liver, rep1 |
| GSM1819922 |
Naive CD8 T cells, spleen, rep2 |
| GSM1819923 |
LCMV central memory CD8 T cells, spleen, rep2 |
| GSM1819924 |
LCMV effector memory CD8 T cells, spleen, rep2 |
| GSM1819925 |
LCMV effector memory CD8 T cells, liver, rep2 |
| GSM1819926 |
LCMV tissue-resident memory CD8 T cells, liver, rep2 |
| GSM1819927 |
LCMV tissue-resident memory CD8 T cells, gut, rep2 |
| GSM1819928 |
LCMV conventional nature killer cells, liver, rep2 |
| GSM1819929 |
LCMV tissue-resident nature killer cells, liver, rep2 |
| GSM1819930 |
LCMV nature killer T cells, liver, rep2 |
| GSM1819931 |
Naive CD8 T cells, spleen, rep3 |
| GSM1819932 |
Naive CD8 T cells, spleen, rep4 |
| GSM1819933 |
HSV tissue-resident memory CD8 T cells, skin, rep1 |
| GSM1819934 |
HSV tissue-resident memory CD8 T cells, skin, rep2 |
| GSM1819935 |
HSV central memory CD8 T cells, spleen, rep1 |
| GSM1819936 |
HSV central memory CD8 T cells, spleen, rep2 |
| GSM1819937 |
HSV effector memory CD8 T cells, spleen, rep1 |
| GSM1819938 |
HSV effector memory CD8 T cells, spleen, rep2 |
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| Relations |
| BioProject |
PRJNA289626 |
| SRA |
SRP060705 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE70813_RAW.tar |
15.1 Mb |
(http)(custom) |
TAR (of TXT) |
| GSE70813_Supp_Raw_Counts.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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