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Spatial cancer systems biology resolves heterotypic interactions and identifies disruption of spatial hierarchy as a pathological driver event

Spatially annotated single-cell datasets provide unprecedented opportunities to dissect cell-cell communication in development and disease. Heterotypic signaling includes interactions between different cell types and is well established in tissue development and spatial organization. Epithelial orga...

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Autor principal: Filipp, Fabian V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10054974/
https://www.ncbi.nlm.nih.gov/pubmed/36993709
http://dx.doi.org/10.1101/2023.03.01.530706
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author Filipp, Fabian V.
author_facet Filipp, Fabian V.
author_sort Filipp, Fabian V.
collection PubMed
description Spatially annotated single-cell datasets provide unprecedented opportunities to dissect cell-cell communication in development and disease. Heterotypic signaling includes interactions between different cell types and is well established in tissue development and spatial organization. Epithelial organization requires several different programs that are tightly regulated. Planar cell polarity (PCP) is the organization of epithelial cells along the planar axis, orthogonal to the apical-basal axis. Here, we investigate PCP factors and explore the implications of developmental regulators as malignant drivers. Utilizing cancer systems biology analysis, we derive a gene expression network for WNT-ligands (WNT) and their cognate frizzled (FZD) receptors in skin cutaneous melanoma. The profiles supported by unsupervised clustering of multiple-sequence alignments identify ligand-independent signaling and implications for metastatic progression based on the underpinning developmental spatial program. Omics studies and spatial biology connect developmental programs with oncological events and explain key spatial features of metastatic aggressiveness. Dysregulation of prominent PCP factors such as specific representatives of the WNT and FZD families in malignant melanoma recapitulates the development program of normal melanocytes but in an uncontrolled and disorganized fashion.
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spelling pubmed-100549742023-03-30 Spatial cancer systems biology resolves heterotypic interactions and identifies disruption of spatial hierarchy as a pathological driver event Filipp, Fabian V. bioRxiv Article Spatially annotated single-cell datasets provide unprecedented opportunities to dissect cell-cell communication in development and disease. Heterotypic signaling includes interactions between different cell types and is well established in tissue development and spatial organization. Epithelial organization requires several different programs that are tightly regulated. Planar cell polarity (PCP) is the organization of epithelial cells along the planar axis, orthogonal to the apical-basal axis. Here, we investigate PCP factors and explore the implications of developmental regulators as malignant drivers. Utilizing cancer systems biology analysis, we derive a gene expression network for WNT-ligands (WNT) and their cognate frizzled (FZD) receptors in skin cutaneous melanoma. The profiles supported by unsupervised clustering of multiple-sequence alignments identify ligand-independent signaling and implications for metastatic progression based on the underpinning developmental spatial program. Omics studies and spatial biology connect developmental programs with oncological events and explain key spatial features of metastatic aggressiveness. Dysregulation of prominent PCP factors such as specific representatives of the WNT and FZD families in malignant melanoma recapitulates the development program of normal melanocytes but in an uncontrolled and disorganized fashion. Cold Spring Harbor Laboratory 2023-03-19 /pmc/articles/PMC10054974/ /pubmed/36993709 http://dx.doi.org/10.1101/2023.03.01.530706 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Filipp, Fabian V.
Spatial cancer systems biology resolves heterotypic interactions and identifies disruption of spatial hierarchy as a pathological driver event
title Spatial cancer systems biology resolves heterotypic interactions and identifies disruption of spatial hierarchy as a pathological driver event
title_full Spatial cancer systems biology resolves heterotypic interactions and identifies disruption of spatial hierarchy as a pathological driver event
title_fullStr Spatial cancer systems biology resolves heterotypic interactions and identifies disruption of spatial hierarchy as a pathological driver event
title_full_unstemmed Spatial cancer systems biology resolves heterotypic interactions and identifies disruption of spatial hierarchy as a pathological driver event
title_short Spatial cancer systems biology resolves heterotypic interactions and identifies disruption of spatial hierarchy as a pathological driver event
title_sort spatial cancer systems biology resolves heterotypic interactions and identifies disruption of spatial hierarchy as a pathological driver event
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10054974/
https://www.ncbi.nlm.nih.gov/pubmed/36993709
http://dx.doi.org/10.1101/2023.03.01.530706
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