Molecular regulators of chemotaxis in human hematopoietic stem cells

Hematopoietic stem cells (HSCs), essential for lifelong blood cell regeneration, are clinically utilized to treat various hematological disorders. These cells originate in the aorta-gonad-mesonephros region, expand in the fetal liver, and mature in the bone marrow. Chemotaxis, involving gradient sensing, polarization, and migration, directs HSCs and is crucial for their homing and mobilization. The molecular regulation of HSC chemotaxis involves chemokines, chemokine receptors, signaling pathways, and cytoskeletal proteins. Recent advances in understanding these regulatory mechanisms have deepened insights into HSC development and hematopoiesis, offering new avenues for therapeutic innovations. Strategies including glucocorticoid receptor activation, modulation of histone acetylation, stimulation of nitric oxide signaling, and interference with m6A RNA modification have shown potential in enhancing CXCR4 expression, thereby improving the chemotactic response and homing capabilities of human HSCs. This review synthesizes current knowledge on the molecular regulation of human HSC chemotaxis and its implications for health and disease.