Fate of hematopoietic stem cells determined by Notch1 signaling (Review)

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.

Prenatal DEHP Exposure Induces Premature Testicular Aging by Promoting Leydig Cell Senescence through the MAPK Signaling Pathways

“…We also found that senescence 𝛽-Gal staining in testes was mainly concentrated in LCs and not spermatogenic tissue. Considering that LCs play a core role in maintaining reproductive and endocrine functions, [36,37] we concluded that prenatal DEHP exposure induced testicular aging by promoting LC senescence.…”

Circulating Notch1 in response to altered vascular wall shear stress in adults

“…Notch1 and its ligands are part of an evolutionarily conserved signalling pathway that is essential for endothelial cell-fate determination (Artavanis-Tsakonas et al, 1999). The Notch signalling pathway has been implicated in a variety of roles including angiogenesis (Hyun et al, 2022), neurogenesis (Wang et al, 2009), limb development (Francis et al, 2005) and haematopoiesis (Ge et al, 2021), but its role as a mechanosensor has only recently been defined (Mack et al, 2017). Through a series of in vitro and in vivo murine knockdown models, Mack et al (2017) demonstrated that Notch1 was responsible for cell elongation, alignment, junctional integrity and endothelial quiescence in response to laminar flow (Mack et al, 2017).…”