Differential requirements for Wnt and Notch signaling in hematopoietic versus thymic niches.
All blood cells are derived from multipotent stem cells, the so-called hematopoietic stem cells (HSCs), that in adults reside in the bone marrow. Most types of blood cells also develop there, with the notable exception of T lymphocytes that develop in the thymus. For both HSCs and developing T cells, interactions with the surrounding microenvironment are critical in regulating maintenance, differentiation, apoptosis, and proliferation. Such specialized regulatory microenvironments are referred to as niches and provide both soluble factors as well as cell-cell interactions between niche component cells and blood cells. Two pathways that are critical for early T cell development in the thymic niche are Wnt and Notch signaling. These signals also play important but controversial roles in the HSC niche. Here, we review the differences and similarities between the thymic and hematopoietic niches, with particular focus on Wnt and Notch signals, as well as the latest insights into regulation of these developmentally important pathways.
Department of Immunohematology and Blood Transfusion (IHB), Leiden University Medical Center, Leiden, the Netherlands.
Paul P C
PP
Roozen
Martijn H
MH
Brugman
Frank J T
FJ
Staal
D000818:Animals; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008954:Models, Biological; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D055153:Stem Cell Niche; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism; D060449:Wnt Signaling Pathway
D016207:Cytokines; D051880:Receptors, Notch