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

Autor:	Groppa E; 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., Martini P; Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy; Department of Biology, University of Padova, via U. Bassi 58B, Padova, Italy., Derakhshan N; School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, Canada., Theret M; School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, Canada., Ritso M; School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, Canada., Tung LW; School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, Canada., Wang YX; Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA., Soliman H; 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., Hamer MS; School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, Canada., Stankiewicz L; School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, Canada., Eisner C; School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, Canada., Erwan LN; Department of Pediatrics, Université Laval, Laval, QC, Canada., Chang C; School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, Canada., Yi L; School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, Canada., Yuan JH; School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, Canada., Kong S; School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, Canada., Weng C; School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, Canada., Adams J; School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, Canada., Chang L; School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, Canada., Peng A; School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, Canada., Blau HM; Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA., Romualdi C; Department of Biology, University of Padova, via U. Bassi 58B, Padova, Italy., Rossi FMV; School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, Canada. Electronic address: fabio@brc.ubc.ca.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2023 Feb 28; Vol. 42 (2), pp. 112051. Date of Electronic Publication: 2023 Jan 31.
DOI:	10.1016/j.celrep.2023.112051
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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