Epigenetische Prägung von Gewebe- und Mikrobiota-abhängigen immunmodulatorischen Eigenschaften in darmdrainierenden Lymphknotenstromazellen

• Antragsteller: Dr. Jörn Pezoldt
• Fachliche Zuordnung: Immunologie ; Bioinformatik und Theoretische Biologie
• Förderung: Förderung von 2018 bis 2019
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 397151636

• Erstellungsjahr: 2019

Zusammenfassung der Projektergebnisse

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.

Projektbezogene Publikationen (Auswahl)

• 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; Bode, Ulrike; Pabst, Oliver; Bajénoff, Marc; Saliba, Antoine-Emmanuel; Huehn, Jochen