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| Status |
Public on Nov 03, 2020 |
| Title |
Single cell RNA-seq (smartseq2) analysis of the ETP population from E15.5 embryonic thymus of the 5x polychromILC mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
ILC2 contribute to immune homeostasis, protective immunity and tissue repair. However, an understanding of the microenvironmental factors and transcriptional circuits that support development of these innate lymphocytes within lymphoid organs, alongside their adaptive T and B cell relatives, is only starting to emerge. Here we demonstrate that functional ILC2 arise in the embryonic thymus, from shared T cell precursors, and precede the emergence of CD4+CD8+ (double-positive) T cells. Strikingly, RORa expression repressed T cell development, whilst promoting ILC2 in the thymus. Thymic ILC2 go on to contribute to the innate type-2 response at mucosal tissues with preferential colonisation of the intestinal lamina propria. From RNAseq, ATACseq and ChIPseq data we propose a revised transcriptional circuit to explain the enigmatic co-development of T cells, ILC2 and NK cells from common progenitors in the thymus. When Notch signalling is present, Bcl11b dampens Nfil3/Id2 expression, permitting E protein-directed T cell commitment. However, concomitant expression of RORa overrides the Nfil3/Id2 repression, allowing Id2 to repress E proteins and promote ILC2 differentiation. Thus, we demonstrate that RORa expression represents a critical checkpoint at the bifurcation of the T cell and ILC2 lineages in the embryonic thymus.
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| Overall design |
Single cell RNA-seq analysis of the ETP population from E15.5 embryonic thymus of the 5x polychromILC mice
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| Contributor(s) |
Ferreira AC, Walker JA, Clark PA, Crisp A, Barlow JL, Heycock M, Kitching S, Lim A, Gogoi M, Szeto A, Berks R, Daly M, Jolin HE, McKenzie AJ |
| Citation(s) |
33432227 |
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| Submission date |
Mar 10, 2020 |
| Last update date |
Feb 03, 2021 |
| Contact name |
Alastair Crisp |
| Organization name |
MRC Laboratory of Molecular Biology
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| Street address |
Francis Crick Avenue
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| City |
Cambridge |
| ZIP/Postal code |
CB2 0QH |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (300)
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| This SubSeries is part of SuperSeries: |
| GSE146745 |
RORa expression is a critical checkpoint for the bifurcation of the T cell and ILC2 lineages in the embryonic thymus |
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| Relations |
| BioProject |
PRJNA611798 |
| SRA |
SRP252231 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE146740_thymus_R_sce_object.rds.gz |
109.0 Mb |
(ftp)(http) |
RDS |
| GSE146740_thymus_single_cell_expression_matrix.tsv.gz |
18.3 Mb |
(ftp)(http) |
TSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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