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

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

doi:10.1016/j.isci.2022.104306

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

Laura A. Tiemeijer (Corresponding author), Tommaso Ristori (Corresponding author), Oscar M.J.A. Stassen, Jaakko J. Ahlberg, Jonne J.J. de Bijl, Christopher S. Chen, Katie Bentley, Carlijn V.C. Bouten, Cecilia M. Sahlgren (Corresponding author)

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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.

Originele taal-2	Engels
Artikelnummer	104306
Aantal pagina's	20
Tijdschrift	iScience
Volume	25
Nummer van het tijdschrift	5
DOI's	https://doi.org/10.1016/j.isci.2022.104306
Status	Gepubliceerd - 20 mei 2022

Bibliografische nota

Publisher Copyright:
© 2022 The Author(s)

Financiering

Funding: this study was supported by the Academy of Finland , grant numbers 307133 , 316882 , and 330411 (LAT, OMJAS, CMS); the Marie Sklodowska-Curie Global Fellowship , grant number 846617 (to TR); ERC ForceMorph , grant number 771168 (OMJAS, CMS). LAT was supported by the Turku Doctoral Network in Molecular Biosciences at Åbo Akademi University . CSC was supported by NIH ( EB00262 and HL147585 ). KB was supported by the Francis Crick Institute , which receives its core funding from Cancer Research UK ( FC001751 ), the UK Medical Research Council ( FC001751 ), and the Wellcome Trust ( FC001751 ). We gratefully acknowledge the Gravitation Program “Materials Driven Regeneration”, funded by the Netherlands Organisation for Scientific Research ( 024.003.013 ) (CVB), the InFLAMES Flagship Program of the Academy of Finland ( 337531 ) (LAT, CMS), and the Åbo Akademi University Foundation’s Center of Excellence in Cellular Mechanostasis (CellMech) (CMS). Funding: this study was supported by the Academy of Finland, grant numbers 307133, 316882, and 330411 (LAT, OMJAS, CMS); the Marie Sklodowska-Curie Global Fellowship, grant number 846617 (to TR); ERC ForceMorph, grant number 771168 (OMJAS, CMS). LAT was supported by the Turku Doctoral Network in Molecular Biosciences at Åbo Akademi University. CSC was supported by NIH (EB00262 and HL147585). KB was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001751), the UK Medical Research Council (FC001751), and the Wellcome Trust (FC001751). We gratefully acknowledge the Gravitation Program “Materials Driven Regeneration”, funded by the Netherlands Organisation for Scientific Research (024.003.013) (CVB), the InFLAMES Flagship Program of the Academy of Finland (337531) (LAT, CMS), and the Åbo Akademi University Foundation's Center of Excellence in Cellular Mechanostasis (CellMech) (CMS). Conceptualization: LAT, TR, CMS. Formal Analyses: LAT, TR, OMJAS. Funding Acquisition: TR, KB, CS, CVCB, CMS. Investigation: LAT, TR, JJJB, JJA, OMJAS. Methodology: LAT, TR, CMS. Project Administration: LAT, TR, CMS. Resources: CSC, CVCB, CMS. Software: TR, JJJB. Supervision: CSC, KB, CVCB, CMS. Validation: LAT, TR, CMS. Visualization: LAT, TR. Writing—Original Draft: LAT, TR. Writing—Review and Editing: LAT, TR, OMJAS, CSC, KB, CVCB, CMS. Authors declare that they have no competing interests.

Financiers	Financiernummer
CVCB
JJA
OMJAS
Åbo Akademi University
National Institutes of Health, NIH	HL147585, EB00262
Wellcome Trust
The Francis Crick Institute
European Union’s Horizon Europe research and innovation programme	771168
H2020 Marie Skłodowska-Curie Actions	846617
Medical Research Council
Cancer Research UK	FC001751
European Research Council
Academy of Finland	307133, 330411, 316882
Nederlandse Organisatie voor Wetenschappelijk Onderzoek	337531, 024.003.013
China Scholarship Council
Åbo Akademi University
Åbo Akademi University

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10.1016/j.isci.2022.104306

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Fluorescence microscopy, image analysis and quantitative PCR data underlying the publication “Engineered patterns of Notch ligands Jag1 and Dll4 elicit differential spatial control of endothelial sprouting”
Tiemeijer, L. A. (Ontwerper), Ristori, T. (Ontwerper), Stassen, O. M. J. A. (Ontwerper), Ahlberg, J. J. (Ontwerper), de Bijl, J. J. J. (Ontwerper), Chen, C. S. (Ontwerper), Bentley, K. (Ontwerper), Bouten, C. V. C. (Ontwerper) & Sahlgren, C. M. (Ontwerper), 4TU.Centre for Research Data, 6 mei 2022
DOI: 10.4121/19235784, https://data.4tu.nl/articles/_/19235784
Dataset
Computational code underlying the publication “Engineered patterns of Notch ligands Jag1 and Dll4 elicit differential spatial control of endothelial sprouting”
Tiemeijer, L. A. (Ontwerper), Ristori, T. (Ontwerper), Stassen, O. M. J. A. (Ontwerper), Ahlberg, J. J. (Ontwerper), de Bijl, J. J. J. (Ontwerper), Chen, C. S. (Ontwerper), Bentley, K. (Ontwerper), Bouten, C. V. C. (Ontwerper) & Sahlgren, C. M. (Ontwerper), 4TU.Centre for Research Data, 6 mei 2022
DOI: 10.4121/19235793, https://data.4tu.nl/articles/_/19235793
Dataset

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title = "Engineered patterns of Notch ligands Jag1 and Dll4 elicit differential spatial control of endothelial sprouting",

abstract = "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.",

keywords = "Bioengineering, Biological sciences, Developmental biology, Tissue engineering",

author = "Tiemeijer, {Laura A.} and Tommaso Ristori and Stassen, {Oscar M.J.A.} and Ahlberg, {Jaakko J.} and {de Bijl}, {Jonne J.J.} and Chen, {Christopher S.} and Katie Bentley and Bouten, {Carlijn V.C.} and Sahlgren, {Cecilia M.}",

note = "Funding Information: Funding: this study was supported by the Academy of Finland , grant numbers 307133 , 316882 , and 330411 (LAT, OMJAS, CMS); the Marie Sklodowska-Curie Global Fellowship , grant number 846617 (to TR); ERC ForceMorph , grant number 771168 (OMJAS, CMS). LAT was supported by the Turku Doctoral Network in Molecular Biosciences at {\AA}bo Akademi University . CSC was supported by NIH ( EB00262 and HL147585 ). KB was supported by the Francis Crick Institute , which receives its core funding from Cancer Research UK ( FC001751 ), the UK Medical Research Council ( FC001751 ), and the Wellcome Trust ( FC001751 ). We gratefully acknowledge the Gravitation Program “Materials Driven Regeneration”, funded by the Netherlands Organisation for Scientific Research ( 024.003.013 ) (CVB), the InFLAMES Flagship Program of the Academy of Finland ( 337531 ) (LAT, CMS), and the {\AA}bo Akademi University Foundation{\textquoteright}s Center of Excellence in Cellular Mechanostasis (CellMech) (CMS). Funding Information: Funding: this study was supported by the Academy of Finland, grant numbers 307133, 316882, and 330411 (LAT, OMJAS, CMS); the Marie Sklodowska-Curie Global Fellowship, grant number 846617 (to TR); ERC ForceMorph, grant number 771168 (OMJAS, CMS). LAT was supported by the Turku Doctoral Network in Molecular Biosciences at {\AA}bo Akademi University. CSC was supported by NIH (EB00262 and HL147585). KB was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001751), the UK Medical Research Council (FC001751), and the Wellcome Trust (FC001751). We gratefully acknowledge the Gravitation Program “Materials Driven Regeneration”, funded by the Netherlands Organisation for Scientific Research (024.003.013) (CVB), the InFLAMES Flagship Program of the Academy of Finland (337531) (LAT, CMS), and the {\AA}bo Akademi University Foundation's Center of Excellence in Cellular Mechanostasis (CellMech) (CMS). Conceptualization: LAT, TR, CMS. Formal Analyses: LAT, TR, OMJAS. Funding Acquisition: TR, KB, CS, CVCB, CMS. Investigation: LAT, TR, JJJB, JJA, OMJAS. Methodology: LAT, TR, CMS. Project Administration: LAT, TR, CMS. Resources: CSC, CVCB, CMS. Software: TR, JJJB. Supervision: CSC, KB, CVCB, CMS. Validation: LAT, TR, CMS. Visualization: LAT, TR. Writing—Original Draft: LAT, TR. Writing—Review and Editing: LAT, TR, OMJAS, CSC, KB, CVCB, CMS. Authors declare that they have no competing interests. ",

year = "2022",

month = may,

day = "20",

doi = "10.1016/j.isci.2022.104306",

language = "English",

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Engineered patterns of Notch ligands Jag1 and Dll4 elicit differential spatial control of endothelial sprouting. / Tiemeijer, Laura A. (Corresponding author); Ristori, Tommaso (Corresponding author); Stassen, Oscar M.J.A. et al.
In: iScience, Vol. 25, Nr. 5, 104306, 20.05.2022.

Onderzoeksoutput: Bijdrage aan tijdschrift › Tijdschriftartikel › Academic › peer review

TY - JOUR

T1 - Engineered patterns of Notch ligands Jag1 and Dll4 elicit differential spatial control of endothelial sprouting

AU - Tiemeijer, Laura A.

AU - Ristori, Tommaso

AU - Stassen, Oscar M.J.A.

AU - Ahlberg, Jaakko J.

AU - de Bijl, Jonne J.J.

AU - Chen, Christopher S.

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N1 - Funding Information: Funding: this study was supported by the Academy of Finland , grant numbers 307133 , 316882 , and 330411 (LAT, OMJAS, CMS); the Marie Sklodowska-Curie Global Fellowship , grant number 846617 (to TR); ERC ForceMorph , grant number 771168 (OMJAS, CMS). LAT was supported by the Turku Doctoral Network in Molecular Biosciences at Åbo Akademi University . CSC was supported by NIH ( EB00262 and HL147585 ). KB was supported by the Francis Crick Institute , which receives its core funding from Cancer Research UK ( FC001751 ), the UK Medical Research Council ( FC001751 ), and the Wellcome Trust ( FC001751 ). We gratefully acknowledge the Gravitation Program “Materials Driven Regeneration”, funded by the Netherlands Organisation for Scientific Research ( 024.003.013 ) (CVB), the InFLAMES Flagship Program of the Academy of Finland ( 337531 ) (LAT, CMS), and the Åbo Akademi University Foundation’s Center of Excellence in Cellular Mechanostasis (CellMech) (CMS). Funding Information: Funding: this study was supported by the Academy of Finland, grant numbers 307133, 316882, and 330411 (LAT, OMJAS, CMS); the Marie Sklodowska-Curie Global Fellowship, grant number 846617 (to TR); ERC ForceMorph, grant number 771168 (OMJAS, CMS). LAT was supported by the Turku Doctoral Network in Molecular Biosciences at Åbo Akademi University. CSC was supported by NIH (EB00262 and HL147585). KB was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001751), the UK Medical Research Council (FC001751), and the Wellcome Trust (FC001751). We gratefully acknowledge the Gravitation Program “Materials Driven Regeneration”, funded by the Netherlands Organisation for Scientific Research (024.003.013) (CVB), the InFLAMES Flagship Program of the Academy of Finland (337531) (LAT, CMS), and the Åbo Akademi University Foundation's Center of Excellence in Cellular Mechanostasis (CellMech) (CMS). Conceptualization: LAT, TR, CMS. Formal Analyses: LAT, TR, OMJAS. Funding Acquisition: TR, KB, CS, CVCB, CMS. Investigation: LAT, TR, JJJB, JJA, OMJAS. Methodology: LAT, TR, CMS. Project Administration: LAT, TR, CMS. Resources: CSC, CVCB, CMS. Software: TR, JJJB. Supervision: CSC, KB, CVCB, CMS. Validation: LAT, TR, CMS. Visualization: LAT, TR. Writing—Original Draft: LAT, TR. Writing—Review and Editing: LAT, TR, OMJAS, CSC, KB, CVCB, CMS. Authors declare that they have no competing interests.

PY - 2022/5/20

Y1 - 2022/5/20

N2 - 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.

AB - 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.

KW - Bioengineering

KW - Biological sciences

KW - Developmental biology

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SN - 2589-0042

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JO - iScience

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

Samenvatting

Bibliografische nota

Financiering

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Datasets

Fluorescence microscopy, image analysis and quantitative PCR data underlying the publication “Engineered patterns of Notch ligands Jag1 and Dll4 elicit differential spatial control of endothelial sprouting”

Computational code underlying the publication “Engineered patterns of Notch ligands Jag1 and Dll4 elicit differential spatial control of endothelial sprouting”

Citeer dit