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. 2021 Jan 21;8:606448. doi: 10.3389/fcell.2020.606448

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Copyright © 2021 Huang, Yang, Ye, Powell and Guo.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Vascular Notch regulation of adult hematopoietic stem cell (HSC) maintenance and regeneration. Canonical Notch signaling involves ligand and receptor binding, Notch receptor subsequent cleavages and release of the Notch intracellular domain (NICD). NICD translocates into the nucleus and turns on RBPJ/NICD-dependent transcription (canonical Notch signaling). RBPJ-independent NICD function is defined as non-canonical Notch signaling. Vascular endothelial cells express Notch ligands Jagged1, Jagged2, Dll1, Dll4, and Notch receptors. Vascular Notch ligand induces Notch downstream target expression within HSCs (cell-autonomous). Notch signaling within endothelial cells could lead to changes in inflammatory signaling and paracrine secretome, including TFN-alpha, GCSF, and KitL, which could then impact HSC behavior cell non-autonomous.