Fate of hematopoietic stem cells determined by Notch1 signaling (Review)
Yidong Ge, Jie Wang, Hui Zhang, Jinyun Li, Meng Ye, Xiaofeng Jin
Abstract
Regulation of the fate of hematopoietic stem cells (HSCs), including silencing, self-renewal or differentiation into blood line cells, is crucial to maintain the homeostasis of the human blood system and prevent leukemia. Notch1, a key receptor in the Notch signaling pathway, plays an important regulatory role in these properties of HSCs, particularly in the maintenance of the stemness of HSCs. In recent decades, the ubiquitination modification of Notch1 has been gradually revealed, and also demonstrated to affect the proliferation and differentiation of HSCs. Therefore, a detailed elucidation of Notch1 and its ubiquitination modification may help to improve understanding of the maintenance of HSC properties and the pathogenesis of leukemia. In addition, it may aid in identifying potential therapeutic targets for specific leukemias and provide potential prognostic indicators for HSC transplantation (HSCT). In the present review, the association between Notch1 and HSCs and the link between the ubiquitination modification of Notch1 and HSCs were described. In addition, the association between abnormal HSCs mediated by Notch1 or ubiquitinated Notch1and T-cell acute lymphoblastic leukemia (T-ALL) was also examined, which provides a promising direction for clinical application.