%0 Journal Article %1 Pezoldt_2022 %A Pezoldt, Joern %A Wiechers, Carolin %A Zou, Mangge %A Litovchenko, Maria %A Biocanin, Marjan %A Beckstette, Michael %A Sitnik, Katarzyna %A Palatella, Martina %A van Mierlo, Guido %A Chen, Wanze %A Gardeux, Vincent %A Floess, Stefan %A Ebel, Maria %A Russeil, Julie %A Arampatzi, Panagiota %A Vafardanejad, Ehsan %A Saliba, Antoine-Emmanuel %A Deplancke, Bart %A Huehn, Jochen %D 2022 %I Springer Science and Business Media LLC %J Nature Communications %K myown %N 1 %R 10.1038/s41467-022-34868-4 %T Postnatal expansion of mesenteric lymph node stromal cells towards reticular and CD34+ stromal cell subsets %U https://doi.org/10.1038%2Fs41467-022-34868-4 %V 13 %X Gut-draining mesenteric lymph nodes (LN) provide the framework to shape intestinal adaptive immune responses. Based on the transcriptional signatures established by our previous work, the composition and immunomodulatory function of LN stromal cells (SC) vary according to location. Here, we describe the single-cell composition and development of the SC compartment within mesenteric LNs derived from postnatal to aged mice. We identify CD34+ SC and fibroblastic reticular stromal cell (FRC) progenitors as putative progenitors, both supplying the typical rapid postnatal mesenteric LN expansion. We further establish the location-specific chromatin accessibility and DNA methylation landscape of non-endothelial SCs and identify a microbiota-independent core epigenomic signature, showing characteristic differences between SCs from mesenteric and skin-draining peripheral LNs. The epigenomic landscape of SCs points to dynamic expression of Irf3 along the differentiation trajectories of FRCs. Accordingly, a mesenchymal stem cell line acquires a Cxcl9+ FRC molecular phenotype upon lentiviral overexpression of Irf3, and the relevance of Irf3 for SC biology is further underscored by the diminished proportion of Ccl19+ and Cxcl9+ FRCs in LNs of Irf3-/- mice. Together, our data constitute a comprehensive transcriptional and epigenomic map of mesenteric LNSC development in early life and dissect location-specific, microbiota-independent properties of non-endothelial SCs.

@article{Pezoldt_2022, abstract = {Gut-draining mesenteric lymph nodes (LN) provide the framework to shape intestinal adaptive immune responses. Based on the transcriptional signatures established by our previous work, the composition and immunomodulatory function of LN stromal cells (SC) vary according to location. Here, we describe the single-cell composition and development of the SC compartment within mesenteric LNs derived from postnatal to aged mice. We identify CD34+ SC and fibroblastic reticular stromal cell (FRC) progenitors as putative progenitors, both supplying the typical rapid postnatal mesenteric LN expansion. We further establish the location-specific chromatin accessibility and DNA methylation landscape of non-endothelial SCs and identify a microbiota-independent core epigenomic signature, showing characteristic differences between SCs from mesenteric and skin-draining peripheral LNs. The epigenomic landscape of SCs points to dynamic expression of Irf3 along the differentiation trajectories of FRCs. Accordingly, a mesenchymal stem cell line acquires a Cxcl9+ FRC molecular phenotype upon lentiviral overexpression of Irf3, and the relevance of Irf3 for SC biology is further underscored by the diminished proportion of Ccl19+ and Cxcl9+ FRCs in LNs of Irf3-/- mice. Together, our data constitute a comprehensive transcriptional and epigenomic map of mesenteric LNSC development in early life and dissect location-specific, microbiota-independent properties of non-endothelial SCs.}, added-at = {2023-02-14T18:13:47.000+0100}, author = {Pezoldt, Joern and Wiechers, Carolin and Zou, Mangge and Litovchenko, Maria and Biocanin, Marjan and Beckstette, Michael and Sitnik, Katarzyna and Palatella, Martina and van Mierlo, Guido and Chen, Wanze and Gardeux, Vincent and Floess, Stefan and Ebel, Maria and Russeil, Julie and Arampatzi, Panagiota and Vafardanejad, Ehsan and Saliba, Antoine-Emmanuel and Deplancke, Bart and Huehn, Jochen}, biburl = {https://www.bibsonomy.org/bibtex/2e6d01b612f137a0b6b06449be093cf69/cusysmed}, day = 24, doi = {10.1038/s41467-022-34868-4}, interhash = {7dc6c5e0ff01c6aa8684d485632889fa}, intrahash = {e6d01b612f137a0b6b06449be093cf69}, journal = {Nature Communications}, keywords = {myown}, month = nov, number = 1, publisher = {Springer Science and Business Media LLC}, timestamp = {2024-04-16T16:26:57.000+0200}, title = {Postnatal expansion of mesenteric lymph node stromal cells towards reticular and CD34+ stromal cell subsets}, type = {Publication}, url = {https://doi.org/10.1038%2Fs41467-022-34868-4}, volume = 13, year = 2022 }