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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 [BRB-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Gut-draining mesenteric lymph nodes (mLNs) provide the framework to shape intestinal adaptive immune responses. We previously delineated transcriptional signatures in LN stromal cells (SC), pointing to tissue-specific variability in SC composition and immunomodulatory function. Here, using scRNA-seq we dissected the developmental trajectory of SCs within mLNs derived from postnatal to aged mice, and identified two putative progenitors, namely CD34+ SC and fibroblastic reticular stromal cell (FRC) progenitors, which both feed the rapid LN expansion postnatally. We further unraveled the tissue-specific chromatin accessibility and DNA methylation landscape of non-endothelial SCs, and identified a microbiota-independent core epigenomic signature, showcasing differences between SCs from mLN and skin-draining peripheral LN. Irf3 was inferred from the epigenomic landscape of SCs, being dynamically expressed along the differentiation trajectories of FRCs. Lentiviral overexpression of Irf3 in a mesenchymal stem cell line established a Cxcl9+ FRC molecular phenotype. The relevance of Irf3 for SC biology was further underscored by the diminished proportion of Ccl19+ and Cxcl9+ FRCs in LNs from Irf3-/- mice. Together, our data constitute a comprehensive transcriptional and epigenomic map of LNSC development in early life and dissect location-specific, microbiota-independent properties of non-endothelial SCs.
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| |
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| Overall design |
3'RNA-seq (methods used BRB-seq) on C3H10T1/2 lentivirally transduced with indicated transcription factor.
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| |
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| Contributor(s) |
Pezoldt J, Biocanin M, Chen W, Deplancke B |
| Citation(s) |
36433946 |
| |
| Submission date |
Apr 12, 2021 |
| Last update date |
Jan 09, 2023 |
| Contact name |
Joern Pezoldt |
| E-mail(s) |
jorn.pezoldt@epfl.ch
|
| Phone |
0041766040171
|
| Organization name |
EPFL
|
| Department |
SV
|
| Lab |
Laboratory Systems Biology and Genetics
|
| Street address |
Station 19, SV 3818.A
|
| City |
Lausanne |
| ZIP/Postal code |
1015 |
| Country |
Switzerland |
| |
|
| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (39)
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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 |
|
| Relations |
| BioProject |
PRJNA721377 |
| SRA |
SRP314465 |
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