Notch Signaling in the Bone Marrow Lymphopoietic Niche

Abstract

Lifelong mammalian hematopoiesis requires continuous generation of mature blood cells that originate from Hematopoietic Stem and Progenitor Cells (HSPCs) situated in the post-natal Bone Marrow (BM). The BM microenvironment is inherently complex and extensive studies have been devoted to identifying the niche that maintains HSPC homeostasis and supports hematopoietic potential. The Notch signaling pathway is required for the emergence of the definitive Hematopoietic Stem Cell (HSC) during embryonic development, but its role in BM HSC homeostasis is convoluted. Recent work has begun to explore novel roles for the Notch signaling pathway in downstream progenitor populations. In this review, we will focus an important role for Notch signaling in the establishment of a T cell primed sub-population of Common Lymphoid Progenitors (CLPs). Given that its activation mechanism relies primarily on cell-to-cell contact, Notch signaling is an ideal means to investigate and define a novel BM lymphopoietic niche. We will discuss how new genetic model systems indicate a pre-thymic, BM-specific role for Notch activation in early T cell development and what this means to the paradigm of lymphoid lineage commitment. Lastly, we will examine how leukemic T-cell acute lymphoblastic leukemia (T-ALL) blasts take advantage of Notch and downstream lymphoid signals in the pathological BM niche.