Hematopoietic stem cell (HSC) self-renewal pathway (HSC self-renewal pathway)

The hematopoietic stem cell (HSC) self-renewal pathway refers to the integrated network of intrinsic and extrinsic signals that govern the ability of HSCs to undergo symmetric or asymmetric divisions while maintaining their undifferentiated state. This pathway is critical for lifelong hematopoiesis, ensuring a steady supply of all blood lineages while preventing the exhaustion of the stem cell reservoir [PubMed: 18295574]. Key molecular drivers include the Wnt, Notch, and Hedgehog signaling pathways, which interact with epigenetic regulators such as the Polycomb group protein BMI1 to control the cell cycle and suppress differentiation programs [PubMed: 16264493, PubMed: 12736680]. In clinical contexts, the pathway is a major focus for ex vivo expansion of cord blood-derived HSCs using small molecules like UM171 and StemRegenin 1 (SR1) to improve transplantation outcomes [PubMed: 25236466, PubMed: 20688917]. Conversely, aberrant activation of self-renewal genes is a primary driver of leukemogenesis, making components of this pathway attractive targets for eliminating leukemic stem cells in myeloid and lymphoid malignancies [PubMed: 15175761].

Other names

HSC self-renewalHematopoietic stem cell maintenanceHSC homeostasis

Modulation of signaling cascades (Wnt, Notch, Hedgehog, or epigenetic regulators like BMI1) to control the balance between self-renewal and differentiation [PubMed: 16264493, PubMed: 12736680].