M-CSF is an important hematopoietic growth factor that acts on hematopoiesis by promoting the growth of monocyte/macrophage colonies from human blood CD34+ progenitor cells and high proliferation colony-forming cells. It can also stimulate the macrophagic production of numerous hematopoietic cytokines (GM-CSF, G-CSF, IL-1, 6, 8, etc). In clinical trial, M-CSF can accelerate the recovery of the hematopoiesis directly or in synergy with other hematopoietic cytokines. M-CSF can also potentiate the ability of mature mononuclear phagocytes to perform their differentiated functions by enhancing their ability to kill infectious microorganisms and tumor cells.
Lineage-specific cytokines such as M-CSF can be strongly induced during physiological stress or infection and potently increase the production of mature cells from lineage committed progenitors. It was also shown that M-CSF can directly induce the myeloid master regulator PU.1 and instruct myeloid cell-fate change in mouse haematopoietic stem cells, independently of selective survival or proliferation. Video imaging and single-cell gene expression analysis revealed that stimulation of highly purified haematopoietic stem cells with M-CSF in culture resulted in activation of the PU.1 promoter and an increased number of PU.1+ cells with myeloid gene signature and differentiation potential. In vivo, high systemic levels of M-CSF directly stimulated M-CSF-receptor-dependent activation of endogenous PU.1 protein in single haematopoietic stem cells and induced a PU.1-dependent myeloid differentiation preference.
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