Engineered patterns of Notch ligands Jag1 and Dll4 elicit differential spatial control of endothelial sprouting

Laura Tiemeijer, Tommaso Ristori, Oscar Stassen, Jaakko Ahlberg, Jonne J.J. de Bijl, Christopher S. Chen, Katie Bentley, Carlijn V.C. Bouten, Cecilia Sahlgren*

*Tämän työn vastaava kirjoittaja

Tutkimustuotos: LehtiartikkeliArtikkeliTieteellinenvertaisarvioitu

1 Lataukset (Pure)

Abstrakti

Spatial regulation of angiogenesis is important for the generation of functional engineered vasculature in regenerative medicine. The Notch ligands Jag1 and Dll4 show distinct expression patterns in endothelial cells and, respectively, promote and inhibit endothelial sprouting. Therefore, patterns of Notch ligands may be utilized to spatially control sprouting, but their potential and the underlying mechanisms of action are unclear. Here, we coupled in vitro and in silico models to analyze the ability of micropatterned Jag1 and Dll4 ligands to spatially control endothelial sprouting. Dll4 patterns, but not Jag1 patterns, elicited spatial control. Computational simulations of the underlying signaling dynamics suggest that different timing of Notch activation by Jag1 and Dll4 underlie their distinct ability to spatially control sprouting. Hence, Dll4 patterns efficiently direct the sprouts, whereas longer exposure to Jag1 patterns is required to achieve spatial control. These insights in sprouting regulation offer therapeutic handles for spatial regulation of angiogenesis.

AlkuperäiskieliEnglanti
Artikkeli104306
JulkaisuiScience
Vuosikerta25
Numero5
DOI - pysyväislinkit
TilaJulkaistu - 20 toukok. 2022
OKM-julkaisutyyppiA1 Julkaistu artikkeli, soviteltu

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