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CSF-1-induced Src signaling can instruct monocytic lineage choice.

Blood 129, 1691-1701 (2017)
Publishers Version Research data DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Controlled regulation of lineage decisions is imperative for hematopoiesis. Yet, the molecular mechanisms underlying hematopoietic lineage choices are poorly defined. CSF-1, the cytokine acting as the principal regulator of monocyte/macrophage development, has been shown to be able to instruct the lineage choice of uncommitted granulocyte macrophage progenitors towards a monocyte/macrophage fate. However, the intracellular signaling pathways involved are unknown. CSF-1 activates a multitude of signaling pathways resulting in a pleiotropic cellular response. The precise role of individual pathways within this complex and redundant signaling network is dependent on cellular context and not well understood. Here, we addressed which CSF-1-activated pathways are involved in transmitting the lineage-instructive signal in primary bone marrow-derived granulocyte macrophage progenitors. While its loss is compensated for by alternative signaling activation mechanisms, Src family kinase signaling is sufficient to transmit the CSF-1 lineage instructive signal. Moreover, c-Src activity is sufficient to drive macrophage fate, even in non-myeloid cells.
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Publication type Article: Journal article
Document type Scientific Article
Reviewing status