Back

Canonical Notch2 Signaling Regulates the Development of Iron-recycling Macrophages and Iron Homeostasis

Schroth, F. N.; Kapanadze, T.; Sablotny, S.; Xu, Y.; Chung, B. M.; Deuper, L.; Kispert, A.; Lochner, M.; Kempf, T.; Haller, H.; Schmidt-Ott, K. M.; Gamrekelashvili, J.; Limbourg, F.

2024-11-15 immunology
10.1101/2024.11.13.622461 bioRxiv
Show abstract

Red pulp macrophages (RPM) and bone marrow macrophages (BMM) are iron-recycling cells involved in iron homeostasis and erythropoiesis. Here, we show, using conditional deletion strategies of Notch signaling components, that the development of RPM and BMM is regulated by canonical Notch2 signaling. Loss of functional Notch2, or its nuclear mediator Rbpj, causes impairment in RPM and BMM and iron overload in the spleen and bone marrow, while prototypic RPM genes required for iron handling are downregulated. This was accompanied by splenic extramedullary hematopoiesis and changes in splenic microarchitecture. Furthermore, early postnatal transfer of bone marrow and fetal liver progenitors rescued the defects in RPM and BMM and iron overload in a Notch2-dependent manner, demonstrating the potential to restore defective tissue resident macrophage niches by Notch-competent progenitors. Thus, canonical Notch2 is required for development and function of iron-recycling macrophages.

Matching journals

The top 5 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.