In Vivo Mapping of Notch Pathway Activity in Normal and Stress Hematopoiesis

• Notch receptor lineage tracing reveals division of labor during early hematopoiesis
• Signaling through the Notch2-Hes1 axis promotes commitment to the erythroid lineage
• Notch signaling is essential for progenitor response during stress erythropoiesis

SummaryAccumulating evidence suggests that Notch signaling is active at multiple points during hematopoiesis. Until recently, the majority of such studies focused on Notch signaling in lymphocyte differentiation and knowledge of individual Notch receptor roles has been limited due to a paucity of genetic tools available. In this manuscript we generate and describe animal models to identify and fate-map stem and progenitor cells expressing each Notch receptor, delineate Notch pathway activation, and perform in vivo gain- and loss-of-function studies dissecting Notch signaling in early hematopoiesis. These models provide comprehensive genetic maps of lineage-specific Notch receptor expression and activation in hematopoietic stem and progenitor cells. Moreover, they establish a previously unknown role for Notch signaling in the commitment of blood progenitors toward the erythrocytic lineage and link Notch signaling to optimal organismal response to stress erythropoiesis.

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