CSF-1-induced Src signaling can instruct monocytic lineage choice.
Controlled regulation of lineage decisions is imperative for hematopoiesis. Yet, the molecular mechanisms underlying hematopoietic lineage choices are poorly defined. Colony-stimulating factor 1 (CSF-1), the cytokine acting as the principal regulator of monocyte/macrophage (M) development, has been shown to be able to instruct the lineage choice of uncommitted granulocyte M (GM) progenitors toward an M 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 is not well understood. Here, we address which CSF-1-activated pathways are involved in transmitting the lineage-instructive signal in primary bone marrow-derived GM progenitors. Although its loss is compensated for by alternative signaling activation mechanisms, Src family kinase (SFK) signaling is sufficient to transmit the CSF-1 lineage instructive signal. Moreover, c-Src activity is sufficient to drive M fate, even in nonmyeloid cells.
Research Unit Stem Cell Dynamics, Helmholtz Center Munich-German Research Center for Environmental Health, Neuherberg, Germany.|Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule Zurich, Basel, Switzerland.
Max
M
Endele
Research Unit Stem Cell Dynamics, Helmholtz Center Munich-German Research Center for Environmental Health, Neuherberg, Germany.|Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule Zurich, Basel, Switzerland.
Dirk
D
Loeffler
Research Unit Stem Cell Dynamics, Helmholtz Center Munich-German Research Center for Environmental Health, Neuherberg, Germany.|Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule Zurich, Basel, Switzerland.
Konstantinos D
KD
Kokkaliaris
Research Unit Stem Cell Dynamics, Helmholtz Center Munich-German Research Center for Environmental Health, Neuherberg, Germany.|Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule Zurich, Basel, Switzerland.
Oliver
O
Hilsenbeck
Research Unit Stem Cell Dynamics, Helmholtz Center Munich-German Research Center for Environmental Health, Neuherberg, Germany.|Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule Zurich, Basel, Switzerland.
Stavroula
S
Skylaki
Research Unit Stem Cell Dynamics, Helmholtz Center Munich-German Research Center for Environmental Health, Neuherberg, Germany.|Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule Zurich, Basel, Switzerland.
Philipp S
PS
Hoppe
Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany.|Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA; and.
Axel
A
Schambach
Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, New York, NY.
E Richard
ER
Stanley
Research Unit Stem Cell Dynamics, Helmholtz Center Munich-German Research Center for Environmental Health, Neuherberg, Germany.|Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule Zurich, Basel, Switzerland.
Timm
T
Schroeder
D000818:Animals; D019070:Cell Lineage; D002478:Cells, Cultured; D042381:Granulocyte Precursor Cells / Q000166:cytology; D006410:Hematopoiesis; D016173:Macrophage Colony-Stimulating Factor / Q000502:physiology*; D051379:Mice; D009000:Monocytes / Q000166:cytology*; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism*
D016173:Macrophage Colony-Stimulating Factor; D019061:src-Family Kinases