Fig. 1: The role of inflammation in hematopoietic stem cell (HSC) differentiation—Inflammation and antigen stimulation have a number of downstream effects on HSC differentiation.
From: Differentiation therapy for myeloid malignancies: beyond cytotoxicity
Extrinsic stimuli, such as interferon alpha (IFN-α) or lipopolysaccharide (LPS) have been shown to activate toll-like receptors (TLRs) 2, 4, and 9 on HSCs. This can result in secretion of vascular endothelial growth factor (VEGF), which increases endothelial permeability. It also results in intracellular activation of MYD88, leading to downstream activation of TRAF6 and NF-kB. Similarly, aging results in a decrease in miR-146a expression, which can also activate MYD88, TRAF6, and NF-kB. This activation results in autocrine and paracrine signaling through cytokines and chemokines, such as granulocyte colony stimulating factor (G-CSF), interleukin 6 (IL6), and tumor necrosis factor (TNF). In the acute state this results in stress granulopoiesis and terminal myeloid differentiation. Over time, prolonged signaling can result in myeloid skewing and a loss of HSC repopulation potential.
