Regulation of Hematopoietic Stem Cell Dormancy and Quiescence: Insights into Regeneration and Disease

Stem cells are undifferentiated cells capable of self-renewal and differentiation into specialized cell types, forming the foundation of tissue maintenance and repair. In the blood system, this process is known as hematopoiesis. Hematopoietic stem cells (HSCs), positioned at the apex of the hematopoietic hierarchy, have the unique ability to reconstitute the hematopoietic system long-term. HSC stemness is defined by multipotency, allowing differentiation into all blood lineages, and self-renewal, maintaining the stem cell pool. A fundamental property of HSCs is quiescence, which refers to a reversible inactive cell cycle state that preserves their self-renewal potential. Dormant HSCs represent a subset of quiescent stem cells with minimal division rates and the most potent stemness. Dysregulation of dormancy and quiescence is linked to HSC dysfunction. Here, we explore mechanisms regulating HSC dormancy and quiescence under homeostatic and stress conditions. Finally, we describe how factors such as aging, inflammation, and malignancies disrupt these states.