Spatial compartmentalization of signaling imparts source-specific functions on secreted factors

Elena Groppa; Paolo Martini; Nima Derakhshan; Marine Theret; Morten Ritso; Lin Wei Tung; Yu Xin Wang; Hesham Soliman; Mark Stephen Hamer; Laura Stankiewicz; Christine Eisner; Le Nevé Erwan; Chihkai Chang; Lin Yi; Jack H. Yuan; Sunny Kong; Curtis Weng; Josephine Adams; Lucas Chang; Anne Peng; Helen M. Blau; Chiara Romualdi; Fabio M.V. Rossi

Cell Reports (Feb 2023)

Spatial compartmentalization of signaling imparts source-specific functions on secreted factors

Elena Groppa,
Paolo Martini,
Nima Derakhshan,
Marine Theret,
Morten Ritso,
Lin Wei Tung,
Yu Xin Wang,
Hesham Soliman,
Mark Stephen Hamer,
Laura Stankiewicz,
Christine Eisner,
Le Nevé Erwan,
Chihkai Chang,
Lin Yi,
Jack H. Yuan,
Sunny Kong,
Curtis Weng,
Josephine Adams,
Lucas Chang,
Anne Peng,
Helen M. Blau,
Chiara Romualdi,
Fabio M.V. Rossi

Affiliations

Elena Groppa: School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, Canada; Borea Therapeutics, Scuola Internazionale Superiore di Studi Avanzati, Via Bonomea 265, Trieste, Italy
Paolo Martini: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy; Department of Biology, University of Padova, via U. Bassi 58B, Padova, Italy
Nima Derakhshan: School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, Canada
Marine Theret: School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, Canada
Morten Ritso: School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, Canada
Lin Wei Tung: School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, Canada
Yu Xin Wang: Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA
Hesham Soliman: School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, Canada; Faculty of Pharmaceutical Sciences, Minia University, Minia, Egypt; Aspect Biosystems, 1781 W 75th Avenue, Vancouver, BC, Canada
Mark Stephen Hamer: School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, Canada
Laura Stankiewicz: School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, Canada
Christine Eisner: School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, Canada
Le Nevé Erwan: Department of Pediatrics, Université Laval, Laval, QC, Canada
Chihkai Chang: School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, Canada
Lin Yi: School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, Canada
Jack H. Yuan: School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, Canada
Sunny Kong: School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, Canada
Curtis Weng: School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, Canada
Josephine Adams: School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, Canada
Lucas Chang: School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, Canada
Anne Peng: School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, Canada
Helen M. Blau: Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA
Chiara Romualdi: Department of Biology, University of Padova, via U. Bassi 58B, Padova, Italy
Fabio M.V. Rossi: School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, Canada; Corresponding author

Journal volume & issue: Vol. 42, no. 2
p. 112051

Abstract

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Summary: Efficient regeneration requires multiple cell types acting in coordination. To better understand the intercellular networks involved and how they change when regeneration fails, we profile the transcriptome of hematopoietic, stromal, myogenic, and endothelial cells over 14 days following acute muscle damage. We generate a time-resolved computational model of interactions and identify VEGFA-driven endothelial engagement as a key differentiating feature in models of successful and failed regeneration. In addition, the analysis highlights that the majority of secreted signals, including VEGFA, are simultaneously produced by multiple cell types. To test whether the cellular source of a factor determines its function, we delete VEGFA from two cell types residing in close proximity: stromal and myogenic progenitors. By comparing responses to different types of damage, we find that myogenic and stromal VEGFA have distinct functions in regeneration. This suggests that spatial compartmentalization of signaling plays a key role in intercellular communication networks.

CP: Stem cell research

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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