Controller for Maintaining Hematopoietic Stem Cell Stemness: Genetic Information Transmission

Hematopoietic stem cell (HSC) has self-renewal and multilineage differentiation capacities. They sustain lifelong homeostasis and repair of damaged tissues, serving as the core cellular foundation for long-term homeostasis and regenerative repair. Maintaining HSC stemness is essential for normal hematopoiesis; this is not a static property but a dynamically regulated process that directly governs the stable operation of regular hematopoiesis. Recent studies show that HSC quiescence, self-renewal, and lineage differentiation are coordinately controlled by multiple signaling cues. Transcription factor networks, the extracellular matrix, metabolic reprogramming, and epigenetic modifications interact to form a regulatory network that governs stemness maintenance. Under physiological conditions, these factors establish stemness homeostasis; when aberrantly remodeled, they drive diseases such as leukemia and bone marrow failure. This review summarizes the factors that modulate HSC function and stemness during genetic information transmission, and discusses their biological significance. It further elaborates on the regulatory network, compares its distinct patterns in physiological versus pathological states, and explores its translational clinical value. Ultimately, this work aims to provide basic researchers with an integrated conceptual framework and to offer feasible forward-looking strategies for clinical translation.