Vascular Notch Signaling in Stress Hematopoiesis
Open Access
- 21 January 2021
- journal article
- review article
- Published by Frontiers Media SA in Frontiers in Cell and Developmental Biology
Abstract
Canonical Notch signaling is one of the most conserved signaling cascades. It regulates cell proliferation, cell differentiation, and cell fate maintenance in a variety of biological systems during development and cancer (Fortini, 2009; Kopan and Ilagan, 2009; Andersson et al., 2011; Ntziachristos et al., 2014). For the hematopoietic system, during embryonic development, Notch1 is essential for the emergence of hematopoietic stem cells (HSCs) at the aorta-gornado-mesonephro regions of the dorsal aorta. At adult stage, Notch receptors and Notch targets are expressed at different levels in diverse hematopoietic cell types and influence lineage choices. For example, Notch specifies T cell lineage over B cells. However, there has been a long-lasting debate on whether Notch signaling is required for the maintenance of adult HSCs, utilizing transgenic animals inactivating different components of the Notch signaling pathway in HSCs or niche cells. The aims of the current mini-review are to summarize the evidence that disapproves or supports such hypothesis and point at imperative questions waiting to be addressed; hence, some of the seemingly contradictory findings could be reconciled. We need to better delineate the Notch signaling events using biochemical assays to identify direct Notch targets within HSCs or niche cells in specific biological context. More importantly, we call for more elaborate studies that pertain to whether niche cell type (vascular endothelial cells or other stromal cell)-specific Notch ligands regulate the differentiation of T cells in solid tumors during the progression of T-lymphoblastic lymphoma (T-ALL) or chronic myelomonocytic leukemia (CMML). We believe that the investigation of vascular endothelial cells' or other stromal cell types' interaction with hematopoietic cells during homeostasis and stress can offer insights toward specific and effective Notch-related therapeutics.This publication has 111 references indexed in Scilit:
- Endothelial Jagged-1 Is Necessary for Homeostatic and Regenerative HematopoiesisCell Reports, 2013
- Dynamic binding of RBPJ is determined by Notch signaling statusGenes & Development, 2013
- Non-canonical Notch signaling: emerging role and mechanismTrends in Cell Biology, 2012
- Genome-wide analysis reveals conserved and divergent features of Notch1/RBPJ binding in human and murine T-lymphoblastic leukemia cellsProceedings of the National Academy of Sciences of the United States of America, 2011
- A novel tumour-suppressor function for the Notch pathway in myeloid leukaemiaNature, 2011
- Endothelial Cells Are Essential for the Self-Renewal and Repopulation of Notch-Dependent Hematopoietic Stem CellsCell Stem Cell, 2010
- Notch-mediated expansion of human cord blood progenitor cells capable of rapid myeloid reconstitutionNature Medicine, 2010
- The Canonical Notch Signaling Pathway: Unfolding the Activation MechanismCell, 2009
- Notch and Wnt signals cooperatively control cell proliferation and tumorigenesis in the intestineProceedings of the National Academy of Sciences of the United States of America, 2009
- Cross-talk between Tumor and Endothelial Cells Involving the Notch3-Dll4 Interaction Marks Escape from Tumor DormancyCancer Research, 2009