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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Oct 07, 2022 |
| Title |
Postnatal expansion of the lymph node stromal cell pool towards reticular and CD34+ stromal cell subsets [scRNA-seq II] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Gut-draining mesenteric lymph nodes (mLN) provide the framework and microenvironment to shape intestinal adaptive immune responses. We previously delineated transcriptional signatures in LN stromal cells (SC), pointing to tissue-specific variability in composition and immuno-modulatory function of SCs. Here, we dissect the tissue-specific epigenomic DNA accessibility and CpG methylation landscape of LN non-endothelial SCs and identify a microbiota-independent core epigenomic signature of LN SCs. By combined analysis of transcription factor (TF) binding sites together with the gene expression profiles of non-endothelial SCs, we delineated TFs poising skin-draining peripheral LN (pLN) SCs for pro-inflammatory responses. Furthermore, using scRNA-seq, we dissected the developmental trajectory of mLN SCs derived from postnatal to aged mice, identifying two distinct putative progenitors, namely CD34+ SC and fibroblastic reticular stromal cell (FRC) progenitors, which both feed the rapid postnatal LN expansion. Finally, we identified Irf3 as a key differentiation TF inferred from the epigenomic signature of mLN SCs that is dynamically expressed along the differentiation trajectories of FRCs, and validated Irf3 as a regulator of Cxcl9+ FRC differentiation. Together, our data constitute a comprehensive transcriptional and epigenomic map of mLN development and dissect location-specific, microbiota-independent properties of mLN non-endothelial SCs. As such, our findings represent a valuable resource to identify core transcriptional regulators that impinge on the developing mLN early in life, thereby shaping long-lasting intestinal adaptive immune responses.
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| Overall design |
Single cell RNA-seq on FACS-isolated CD45-CD24- mesenteric and skin draining lymph node stromal cells of germ-free mice
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| Contributor(s) |
Pezoldt J, Wiechers C, Litovchenko M, Zou M, Vafardanejad E, Saliba A, Huehn J |
| Citation(s) |
36433946 |
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| Submission date |
Jan 14, 2022 |
| Last update date |
Jan 09, 2023 |
| Contact name |
Joern Pezoldt |
| E-mail(s) |
jorn.pezoldt@epfl.ch
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| Phone |
0041766040171
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| Organization name |
EPFL
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| Department |
SV
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| Lab |
Laboratory Systems Biology and Genetics
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| Street address |
Station 19, SV 3818.A
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| City |
Lausanne |
| ZIP/Postal code |
1015 |
| Country |
Switzerland |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (2) |
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| This SubSeries is part of SuperSeries: |
| GSE172526 |
Postnatal expansion of the lymph node stromal cell pool towards reticular and CD34+ stromal cell subsets |
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| Relations |
| BioProject |
PRJNA797363 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE193705_GF_nonEndoSC.Rds.gz |
1.6 Gb |
(ftp)(http) |
RDS |
| GSE193705_RAW.tar |
51.0 Mb |
(http)(custom) |
TAR (of TAR) |
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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