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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jun 21, 2023 |
| Title |
Thymic epithelial cell potency and fate in early organogenesis assessed by single cell transcriptional and functional analysis [Smart-Seq2] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
During development, cortical (c) and medullary (m) thymic epithelial cells (TEC) arise from the third pharyngeal pouch endoderm. Current models suggest that within the thymic primordium most TEC exist in a bipotent/common thymic epithelial progenitor cell (TEPC) state able to generate both cTEC and mTEC, at least until embryonic day 12.5 (E12.5) in the mouse. This view, however, is challenged by recent transcriptomics and genetic evidence. We therefore set out to investigate the fate and potency of TEC in the early thymus. Here using single cell (sc) RNAseq we identify a candidate mTEC progenitor population at E12.5, consistent with recent reports. Via lineage-tracing we demonstrate this population is mTEC fate-restricted, validating our bioinformatics prediction. Using potency analyses we also establish that most E11.5 and E12.5 progenitor TEC are cTEC-fated. Finally, we show that overnight culture causes most if not all E12.5 cTEC-fated TEPC to acquire functional bipotency and provide a likely molecular mechanism for this changed differentiation potential. Collectively, our data overturn the widely held view that a common TEPC predominates in the E12.5 thymus, showing instead that sublineage-primed progenitors are present from the earliest stages of thymus organogenesis but that these early fetal TEPC exhibit cell-fate plasticity in response to extrinsic factors. Our data provide a significant advance in understanding of fetal thymic epithelial development and thus have implications for thymus-related clinical research, in particular research focussed on generating TEC from pluripotent stem cells.
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| Overall design |
scRNAseq SmartSeq2 profiling of individual EPCAM+PLET1+ cells from E10.5 or E12.5 primordia
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| Contributor(s) |
Chengrui A, Farley AM, Palmer S, Liu D, Kousa AI, Rouse P, Major V, Sweetman J, Morys J, Corsinotti A, Nichols J, Ure J, McLay R, Boulter L, Chapman J, Tomlinson SR, Blackburn CC |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
May 17, 2023 |
| Last update date |
Jul 14, 2023 |
| Contact name |
Catherine Clare Blackburn |
| E-mail(s) |
c.blackburn@ed.ac.uk
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| Phone |
+447810223009
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| Organization name |
University of Edinburgh
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| Department |
School of Biological Sciences
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| Lab |
Thymus generation and regeneration
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| Street address |
IRR North, 5 Little France Drive
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| City |
Edinburgh |
| ZIP/Postal code |
EH16 4UU |
| Country |
United Kingdom |
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| Platforms (1) |
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| Samples (19)
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| GSM7373478 |
E10.5d TEPC, scRNAseq SmartSeq2 |
| GSM7373479 |
Rep E10.5a TEPC, scRNAseq SmartSeq2 |
| GSM7373480 |
Rep E10.5b TEPC, scRNAseq SmartSeq2 |
| GSM7373481 |
Rep E10.5c TEPC, scRNAseq SmartSeq2 |
| GSM7373482 |
Rep E10.5d1 TEPC, scRNAseq SmartSeq2 |
| GSM7373483 |
Rep E10.5d2 TEPC, scRNAseq SmartSeq2 |
| GSM7373484 |
E12.5a TEPC, scRNAseq SmartSeq2 |
| GSM7373485 |
E12.5b TEPC, scRNAseq SmartSeq2 |
| GSM7373486 |
E12.5c TEPC, scRNAseq SmartSeq2 |
| GSM7373487 |
E12.5d TEPC, scRNAseq SmartSeq2 |
| GSM7373488 |
E12.5e TEPC, scRNAseq SmartSeq2 |
| GSM7373489 |
Rep E12.5a TEPC, scRNAseq SmartSeq2 |
| GSM7373490 |
Rep E12.5c TEPC, scRNAseq SmartSeq2 |
| GSM7373491 |
Rep E12.5d TEPC, scRNAseq SmartSeq2 |
| GSM7373492 |
Rep E12.5e1 TEPC, scRNAseq SmartSeq2 |
| GSM7373493 |
Rep E12.5e2 TEPC, scRNAseq SmartSeq2 |
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| Relations |
| BioProject |
PRJNA973716 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE232765_RAW.tar |
130.8 Mb |
(http)(custom) |
TAR (of CSV, PDF, TXT, ZIP) |
| GSE232765_rawcounts.csv.gz |
4.5 Mb |
(ftp)(http) |
CSV |
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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