Definierung des zellulären Ursprungs von Osteoclasten in vivo.
Zusammenfassung der Projektergebnisse
Aim of the project was to understand the origin and turn-over of bone-resorbing osteoclasts in vivo. To this end we exploited an in house generated lineage-tracing mouse tool that specifically targets embryo-derived macrophages and that has been used extensively to understand the generation of osteoclasts during development and their turn-over during life time. We could show that the osteoclast cell pool is established during embryonic development by embryonic but not definitive hematopoietic stem cell-derived macrophages. Further, maintenance of the osteoclast cell pool is ensured through the iterative fusion of hematopoietic stem cell-derived myeloid cells with preexisting embryo-derived osteoclasts. To show potential clinical use we have extended the analysis and have shown that the infusion of myeloid blood cells rescues a late onset model from developing osteopetrosis. These findings suggest that the current clinical practice of using bone marrow transplantation as curative treatment of osteopetrosis may potentially be replaced by the infusion of blood myeloid cells – a procedure that requires much less toxic treatment compared to bone marrow transplantation.
Projektbezogene Publikationen (Auswahl)
-
CSF1R regulates the dendritic cell pool size in adult mice via embryo-derived tissue-resident macrophages. Nature Communications, 9(1).
Percin, Gulce Itir; Eitler, Jiri; Kranz, Andrea; Fu, Jun; Pollard, Jeffrey W.; Naumann, Ronald & Waskow, Claudia
-
Developmental origin, functional maintenance and genetic rescue of osteoclasts. Nature, 568(7753), 541-545.
Jacome-Galarza, Christian E.; Percin, Gulce I.; Muller, James T.; Mass, Elvira; Lazarov, Tomi; Eitler, Jiri; Rauner, Martina; Yadav, Vijay K.; Crozet, Lucile; Bohm, Mathieu; Loyher, Pierre-Louis; Karsenty, Gerard; Waskow, Claudia & Geissmann, Frederic
-
Ontogeny of arterial macrophages defines their functions in homeostasis and inflammation. Nature Communications, 11(1).
Weinberger, Tobias; Esfandyari, Dena; Messerer, Denise; Percin, Gulce; Schleifer, Christian; Thaler, Raffael; Liu, Lulu; Stremmel, Christopher; Schneider, Vanessa; Vagnozzi, Ronald J.; Schwanenkamp, Jennifer; Fischer, Maximilian; Busch, Katrin; Klapproth, Kay; Ishikawa-Ankerhold, Hellen; Klösges, Lukas; Titova, Anna; Molkentin, Jeffery D.; Kobayashi, Yasuhiro ... & Schulz, Christian
