Spatially discrete signalling niches regulate fibroblast heterogeneity in human lung cancer [single-cell RNA-seq]
Spatially discrete signalling niches regulate fibroblast heterogeneity in human lung cancer [single-cell RNA-seq]
Fibroblasts are functionally heterogeneous cells, capable of promoting and suppressing tumour progression. Across cancer types, the extent and cause of this phenotypic diversity remains unknown. We used single-cell RNA sequencing and multiplexed immunohistochemistry to examine fibroblast heterogeneity in human lung and non-small cell lung cancer (NSCLC) samples. This identified seven fibroblast subpopulations: including inflammatory fibroblasts and myofibroblasts (representing terminal differentiation states), quiescent fibroblasts, proto-myofibroblasts (x2) and proto-inflammatory fibroblasts (x2). Fibroblast subpopulations were variably distributed throughout tissues but accumulated at discrete niches associated with differentiation status. Bioinformatics analyses suggested TGF-β1 and IL-1 as key regulators of myofibroblastic and inflammatory differentiation respectively. However, in vitro analyses showed that whilst TGF-β1 stimulation in combination with increased tissue tension could induce myofibroblast marker expression, it failed to fully re-capitulate ex-vivo phenotypes. Similarly, IL-1β treatment only induced upregulation of a subset of inflammatory fibroblast marker genes. In silico modelling of ligand-receptor signalling identified additional pathways and cell interactions likely to be involved in fibroblast activation, This highlighted a potential role for IL-11 and IL-6 (among other ligands) in myofibroblast and inflammatory fibroblast activation respectively. This analysis provides valuable insight into fibroblast subtypes and differentiation mechanisms in NSCLC.
NCBI (National Center for Biotechnology Information) GEO (Gene Expression Omnibus)
Hanley, Christopher
7e2d840d-e724-4389-a362-83741ccdf241
Hanley, Christopher
7e2d840d-e724-4389-a362-83741ccdf241
Hanley, Christopher
(2020)
Spatially discrete signalling niches regulate fibroblast heterogeneity in human lung cancer [single-cell RNA-seq].
NCBI (National Center for Biotechnology Information) GEO (Gene Expression Omnibus)
[Dataset]
Abstract
Fibroblasts are functionally heterogeneous cells, capable of promoting and suppressing tumour progression. Across cancer types, the extent and cause of this phenotypic diversity remains unknown. We used single-cell RNA sequencing and multiplexed immunohistochemistry to examine fibroblast heterogeneity in human lung and non-small cell lung cancer (NSCLC) samples. This identified seven fibroblast subpopulations: including inflammatory fibroblasts and myofibroblasts (representing terminal differentiation states), quiescent fibroblasts, proto-myofibroblasts (x2) and proto-inflammatory fibroblasts (x2). Fibroblast subpopulations were variably distributed throughout tissues but accumulated at discrete niches associated with differentiation status. Bioinformatics analyses suggested TGF-β1 and IL-1 as key regulators of myofibroblastic and inflammatory differentiation respectively. However, in vitro analyses showed that whilst TGF-β1 stimulation in combination with increased tissue tension could induce myofibroblast marker expression, it failed to fully re-capitulate ex-vivo phenotypes. Similarly, IL-1β treatment only induced upregulation of a subset of inflammatory fibroblast marker genes. In silico modelling of ligand-receptor signalling identified additional pathways and cell interactions likely to be involved in fibroblast activation, This highlighted a potential role for IL-11 and IL-6 (among other ligands) in myofibroblast and inflammatory fibroblast activation respectively. This analysis provides valuable insight into fibroblast subtypes and differentiation mechanisms in NSCLC.
This record has no associated files available for download.
More information
Published date: 8 July 2020
Identifiers
Local EPrints ID: 474720
URI: http://eprints.soton.ac.uk/id/eprint/474720
PURE UUID: 54507be9-7e4b-4f8d-9312-86884262dca4
Catalogue record
Date deposited: 01 Mar 2023 18:07
Last modified: 06 May 2023 01:50
Export record
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics
