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Series GSE232765 Query DataSets for GSE232765
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
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.
Overall design scRNAseq SmartSeq2 profiling of individual EPCAM+PLET1+ cells from E10.5 or E12.5 primordia
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
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Submission date May 17, 2023
Last update date Jul 14, 2023
Contact name Catherine Clare Blackburn
Phone +447810223009
Organization name University of Edinburgh
Department School of Biological Sciences
Lab Thymus generation and regeneration
Street address IRR North, 5 Little France Drive
City Edinburgh
ZIP/Postal code EH16 4UU
Country United Kingdom
Platforms (1)
GPL16417 Illumina MiSeq (Mus musculus)
Samples (19)
GSM7373475 E10.5a TEPC, scRNAseq SmartSeq2
GSM7373476 E10.5b TEPC, scRNAseq SmartSeq2
GSM7373477 E10.5c TEPC, scRNAseq SmartSeq2
BioProject PRJNA973716

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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 SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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