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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Oct 13, 2021 |
| Title |
Transcriptional regulation by Aire in medullary thymic epithelial cells revisited |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
The deficiency of Aire, a transcriptional regulator whose defect results in the development of autoimmunity, is associated with reduced expression of tissue-restricted self-Ags (TRAs) in medullary thymic epithelial cells (mTECs). Although the mechanisms underlying Aire-dependent expression of TRAs need to be explored, the physical identification of the target(s) of Aire has been hampered by the low and promiscuous expression of TRAs. We have tackled this issue by engineering mice with augmented Aire expression. Integration of the transcriptomic data from Aire-augmented and Aire-deficient mTECs revealed that a large proportion of so-called Aire-dependent genes, including those of TRAs, may not be direct transcriptional targets downstream of Aire. Rather, Aire induces TRA expression indirectly through controlling the heterogeneity of mTECs, as revealed by single-cell analyses. In contrast, Ccl25 emerged as a canonical target of Aire, and we verified this both in vitro and in vivo. Our approach has illuminated the Aire?s primary targets while distinguishing them from the secondary targets.
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| Overall design |
FACS-sorted mTEChigh from one mouse at eight weeks of age were prepared for scRNA-seq analyses, TECs WT and TECs 3xAireKI.
ATAC-seq analysis for FACS-sorted mTECs from mice at eight weeks of age
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| Contributor(s) |
Nishijima H, Matsumoto M, Miyazawa R, Hosomichi K, Akiyama N, Akiyama T, Tsuneyama K, Morimoto J, Yoshida H, Matsumoto M |
| Citation(s) |
34930780 |
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| Submission date |
Jul 29, 2020 |
| Last update date |
Nov 29, 2022 |
| Contact name |
Hideyuki Yoshida |
| E-mail(s) |
[email protected]
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| Organization name |
RIKEN IMS
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| Street address |
1-7-22 Suehiro-cho
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| City |
Tsurumi-ku, Yokohama |
| State/province |
Kanagawa |
| ZIP/Postal code |
230-0045 |
| Country |
Japan |
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| Platforms (2) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (14)
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| GSM4699226 |
TECs 3xAireKI batch2 |
| GSM4946386 |
TECs control batch1 |
| GSM4946387 |
TECs AireKO batch1 |
| GSM4946388 |
TECs control batch2 |
| GSM4946389 |
TECs AireKO batch2 |
| GSM6304182 |
mTEChi, 3xAireKI, ATAC, rep1 |
| GSM6304183 |
mTEChi, 3xAireKI,ATAC, rep2 |
| GSM6304184 |
mTEClo, 3xAireKI,ATAC, rep1 |
| GSM6304185 |
mTEChi, WT, ATAC, rep1 |
| GSM6304186 |
mTEChi, WT, ATAC, rep2 |
| GSM6304187 |
mTEClo, WT, ATAC, rep1 |
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| Relations |
| BioProject |
PRJNA649427 |
| SRA |
SRP274086 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE155331_RAW.tar |
1.4 Gb |
(http)(custom) |
TAR (of BW, MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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