Notch Receptor-Ligand Engagement Maintains Hematopoietic Stem Cell Quiescence and Niche Retention

• DOI: 10.1002/stem.2031
• Publication Date: 2015-04-07T15:46:07Z
• Authors: Weihuan Wang; Shuiliang Yu; Grant Zimmerman; Yiwei Wang; Jay Myers; Vionnie W. C. Yu; Dan Huang; Xiaoran Huang; Jeongsup Shim; Yuanshuai Huang; William Xin; Peter Qiao; Minhong Yan; Wei Xin; David T. Scadden; Pamela Stanley; John B. Lowe; Alex Y. Huang; Christian W. Siebel; Lan Zhou
• Keywords: Mice; 0303 health sciences; 03 medical and health sciences; Receptors, Notch; Animals; Humans; Stem Cell Niche; Stromal Cells; Hematopoietic Stem Cells; Signal Transduction

Abstract Notch is long recognized as a signaling molecule important for stem cell self-renewal and fate determination. Here, we reveal novel adhesive role of Notch-ligand engagement in hematopoietic progenitor cells (HSPCs). Using mice with conditional loss O-fucosylglycans on EGF-like repeats the binding ligands, report that HSPCs faulty ligand ability display enhanced cycling accompanied by increased egress from marrow, phenotype mainly attributed to their reduced adhesion ligand-expressing stromal osteoblastic altered occupation niches. Adhesion ligand-bearing or inhibits wild type but not O-fucosylglycan-deficient HSPC cycling, independent RBP-JK-mediated canonical signaling. Furthermore, neutralizing antibodies induce RBP-JK-independent mobilization. We, therefore, conclude receptor–ligand controls quiescence retention marrow niche dependent Notch. Stem Cells 2015;33:2280–2293