Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/86832
Title: Enhanced Delta-Notch lateral inhibition model incorporating intracellular notch heterogeneity and tension-dependent rate of Delta-Notch binding that reproduces sprouting angiogenesis patterns
Authors: Koon, Yen Ling
Zhang, Songjing
Koh, Cheng Gee
Chiam, Keng-Hwee
Muhammad Bakhait Rahmat
Keywords: Delta-Notch Lateral Inhibition Model
Intracellular Notch Heterogeneity
Issue Date: 2018
Source: Koon, Y. L., Zhang, S., Muhammad Bakhait Rahmat., Koh, C. G., & Chiam, K.-H. (2018). Enhanced Delta-Notch lateral inhibition model incorporating intracellular notch heterogeneity and tension-dependent rate of Delta-Notch binding that reproduces sprouting angiogenesis patterns. Scientific Reports, 8(1), 9519-.
Series/Report no.: Scientific Reports
Abstract: Endothelial cells adopt unique cell fates during sprouting angiogenesis, differentiating into tip or stalk cells. The fate selection process is directed by Delta-Notch lateral inhibition pathway. Classical Delta-Notch models produce a spatial pattern of tip cells separated by a single stalk cell, or the salt-and-pepper pattern. However, classical models cannot explain alternative tip-stalk patterning, such as tip cells that are separated by two or more stalk cells. We show that lateral inhibition models involving only Delta and Notch proteins can also recapitulate experimental tip-stalk patterns by invoking two mechanisms, specifically, intracellular Notch heterogeneity and tension-dependent rate of Delta-Notch binding. We introduce our computational model and analysis where we establish that our enhanced Delta-Notch lateral inhibition model can recapitulate a greater variety of tip-stalk patterning which is previously not possible using classical lateral inhibition models. In our enhanced Delta-Notch lateral inhibition model, we observe the existence of a hybrid cell type displaying intermediate tip and stalk cells’ characteristics. We validate the existence of such hybrid cells by immuno-staining of endothelial cells with tip cell markers, Delta and CD34, which substantiates our enhanced model.
URI: https://hdl.handle.net/10356/86832
http://hdl.handle.net/10220/45275
ISSN: 2045-2322
DOI: http://dx.doi.org/10.1038/s41598-018-27645-1
Rights: © 2017 The Author(s) (Nature Publishing Group). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Fulltext Permission: open
Fulltext Availability: With Fulltext
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