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| Status |
Public on Apr 30, 2022 |
| Title |
Transcriptome diversity in human medullary thymic epithelial cells - 5'Cap sequencing |
| Organism |
Homo sapiens |
| Experiment type |
Other
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| Summary |
The induction of central T-cell tolerance in the thymus depends on the presentation of peripheral self-epitopes by medullary thymic epithelial cells (mTECs), enabled by a process known as promiscuous gene expression (pGE). Transcriptome diversity generated during pGE has many contributors, including non-canonical transcription initiation, alternative splicing and expression of endogenous retroelements (EREs). However, their significance and regulation are poorly understood in the healthy human thymus. Here, we mapped the expression of genome-wide transcripts in immature and mature human mTECs using high-throughput 5'Cap and RNA sequencing. Overall, 96% of protein coding genes were represented across five human mTEC samples, with mature mTECs showing increased rates of global transcript mis-initiation. Both mTEC populations have increased splicing entropy, which appears to be driven by expression of peripheral splicing factors. Furthermore, EREs enriched in long terminal repeat retrotransposons are up-regulated during mTEC maturation and enriched in genomic proximity to differentially expressed genes. We provide an interactive interface to explore the transcriptome diversity we uncovered at http://transcriptomediversity.cshl.edu/. Our findings represent an important first step towards the generation of a comprehensive map of transcriptome diversity in the healthy human thymus. Ultimately, a complete map of thymic expression diversity will allow for the identification of epitopes that contribute to the pathogenesis of auto-immunity and that drive immune recognition of tumor antigens.
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| Overall design |
Genome-wide transcription start site analysis using 5'Cap sequencing data for human mature (MHCII high) and immature (MHCII) medullary thymic epithelial cells
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| Contributor(s) |
Meyer HV, Carter JA |
| Citation(s) |
35918316 |
| Submission date |
Apr 27, 2022 |
| Last update date |
Aug 16, 2022 |
| Contact name |
Hannah Verena Meyer |
| E-mail(s) |
hmeyer@cshl.edu
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| Organization name |
Cold Spring Harbor Laboratory
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| Street address |
1 Bungtown Road
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| City |
Cold Spring Harbor |
| State/province |
New York |
| ZIP/Postal code |
11724 |
| Country |
USA |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (10)
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| GSM6070085 |
medullary thymic epithelial cells, mature, donor 87 [pt87_hi_5'Cap] |
| GSM6070086 |
medullary thymic epithelial cells, immature, donor 87 [pt87_lo_5'Cap] |
| GSM6070087 |
medullary thymic epithelial cells, mature, donor 212 [pt212_hi_5'Cap] |
| GSM6070088 |
medullary thymic epithelial cells, immature, donor 212 [pt212_lo_5'Cap] |
| GSM6070089 |
medullary thymic epithelial cells, mature, donor 214 [pt214_hi_5'Cap] |
| GSM6070090 |
medullary thymic epithelial cells, immature, donor 214 [pt214_lo_5'Cap] |
| GSM6070091 |
medullary thymic epithelial cells, mature, donor 221 [pt221_hi_5'Cap] |
| GSM6070092 |
medullary thymic epithelial cells, immature, donor 221 [pt221_lo_5'Cap] |
| GSM6070093 |
medullary thymic epithelial cells, mature, donor 226 [pt226_hi_5'Cap] |
| GSM6070094 |
medullary thymic epithelial cells, immature, donor 226 [pt226_lo_5'Cap] |
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| This SubSeries is part of SuperSeries: |
| GSE201720 |
Transcriptome diversity in human medullary thymic epithelial cells |
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| Relations |
| BioProject |
PRJNA832752 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE201718_fivepseq_abundance_tsr.csv.gz |
4.3 Mb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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