Epigenetic imprinting of location- and commensal-dependent immunomodulatory properties in mesenteric lymph node stromal cells
Bioinformatics and Theoretical Biology
Final Report Abstract
Here, we have mapped the variable location-specific epigenetic landscape of lymph node fibroblastic stromal cells. We identified microbiota-independent persistent epigenetically modified genomic loci. Using motif enrichment analysis together with the transcriptional profiles obtained via RNA-sequencing, we delineated steady-state expression signatures poising pLN stromal cells for pro-inflammatory responses and implicate TF modules that regulate the expression of dormant accessible genes in mLN. We further delineate the developmental trajectory of the mLN and concoct subset-specifically expressed TFs to distinct expanding stromal cell populations, implicated to shape the epigenetic landscape across adventitial and reticular fibroblastic stromal cells. Our data constitute a comprehensive map of mesenteric lymph node development and the epigenetic landscape of location-specific properties of lymph node stromal cells, providing a valuable resource to delineate environmental stimuli that impinge on the developing lymph node, permanently shaping immune responses. During the project important improvements in analyzing scRNA-seq data were provided by the scientific community, permitting the applicant to improve ongoing anylsis.
Publications
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Neonatally imprinted stromal cell subsets induce tolerogenic dendritic cells in mesenteric lymph nodes, Nature Communications, 2018, 9,1, 3903
Pezoldt, Joern; Pasztoi, Maria; Zou, Mangge; Wiechers, Carolin; Beckstette, Michael; Thierry, Guilhem R.; Vafadarnejad, Ehsan; Floess, Stefan; Arampatzi, Panagiota; Buettner, Manuela; Schweer, Janina; Fleissner, Diana; Vital, Marius; Pieper, Dietmar H.; Basic, Marijana; Dersch, Petra; Strowig, Till; Hornef, Mathias; Bleich, André; ... & Huehn, Jochen
