Enhanced Delta-Notch Lateral Inhibition Model Incorporating Intracellular Notch Heterogeneity and Tension-Dependent Rate of Delta-Notch Binding that Reproduces Sprouting Angiogenesis Patterns.
Enhanced Delta-Notch Lateral Inhibition Model Incorporating Intracellular Notch Heterogeneity and Tension-Dependent Rate of Delta-Notch Binding that Reproduces Sprouting Angiogenesis Patterns.
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DOI：
10.1038/s41598-018-27645-1
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发表时间：
2018-06-22
影响因子：
4.6
通讯作者：
Chiam KH
中科院分区：
文献类型：
--
作者：
Koon YL;Zhang S;Rahmat MB;Koh CG;Chiam KH
内皮细胞在萌发血管生成过程中采用独特的细胞命运，分化为尖端或柄细胞。其命运选择过程受Delta-Notch侧向抑制途径的指导。经典的Delta-Notch模型产生由单个柄细胞隔开的尖端细胞的空间模式，或盐和胡椒模式。然而，经典模型不能解释另一种顶端-茎模式，例如由两个或更多柄细胞分开的顶端细胞。我们表明，只涉及Delta和Notch蛋白的侧抑制模型也可以通过调用两种机制来概括实验的尖茎模式，特别是细胞内Notch异质性和Delta-Notch结合的张力依赖速率。我们介绍了我们的计算模型和分析，其中我们建立了我们的增强Delta-Notch侧抑制模型可以概括更多种类的尖端-茎模式，这在以前使用经典的侧抑制模型是不可能的。在我们的增强的Delta-Notch侧抑制模型中，我们观察到一种杂交细胞类型的存在，表现出中间的尖端和柄细胞的特征。我们通过用TIP细胞标记物Delta和CD34对内皮细胞进行免疫染色来验证这种杂交细胞的存在，这证实了我们的增强模型。
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.
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DOI：
10.1083/jcb.200407100
发表时间：
2004-12-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ahimou F;Mok LP;Bardot B;Wesley C
通讯作者：
Wesley C
影响因子：
16.6
作者：
Aspalter IM;Gordon E;Dubrac A;Ragab A;Narloch J;Vizán P;Geudens I;Collins RT;Franco CA;Abrahams CL;Thurston G;Fruttiger M;Rosewell I;Eichmann A;Gerhardt H
通讯作者：
Gerhardt H
影响因子：
56.9
作者：
Amonlirdviman, K;Khare, NA;Tomlin, CJ
通讯作者：
Tomlin, CJ
DOI：
10.1038/nrm3176
发表时间：
2011-08-23
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
5.4
作者：
Blanco, Raquel;Gerhardt, Holger
通讯作者：
Gerhardt, Holger