Canonical Notch2 signaling regulates development and maintenance of iron-recycling macrophages and iron homeostasis.

Canonical Notch2 signaling is essential for the development, maintenance, and function of iron-recycling macrophages, with its disruption causing iron overload in mice.

• Why it matters: Understanding how iron-recycling macrophages develop and function is critical for addressing iron homeostasis disorders and related hematological conditions.
• What they did: The study used conditional deletion of Notch signaling components via Cx3cr1Cre in mice, along with antibody treatments and progenitor transfers, to investigate Notch2's role in RPM and BMM development.
• The result: Loss of Notch2 impairs macrophage development, causes iron overload, and alters spleen architecture, while progenitor transfer can rescue these defects, highlighting Notch2's vital regulatory role.