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Review
. 2024 Mar 8:15:1304853.
doi: 10.3389/fgene.2024.1304853. eCollection 2024.

Fibroblast heterogeneity and functions: insights from single-cell sequencing in wound healing, breast cancer, ovarian cancer and melanoma

Omar Lujano Olazaba  1 , Jeffrey Farrow  1 , Teresa Monkkonen  1
Affiliations
Review

Fibroblast heterogeneity and functions: insights from single-cell sequencing in wound healing, breast cancer, ovarian cancer and melanoma

Omar Lujano Olazaba et al. Front Genet. .

Abstract

Cancer has been described as the wound that does not heal, in large part due to fibroblast involvement. Activation of cancer-associated fibroblasts (CAFs) contributes to critical features of the tumor microenvironment, including upregulation of key marker proteins, recruitment of immune cells, and deposition of extracellular matrix (ECM)-similar to fibroblast activation in injury-induced wound healing. Prior to the widespread availability of single-cell RNA sequencing (scRNA seq), studies of CAFs or fibroblasts in wound healing largely relied on models guided by individual fibroblast markers, or methods with less resolution to unravel the heterogeneous nature of CAFs and wound healing fibroblasts (especially regarding scarring outcome). Here, insights from the enhanced resolution provided by scRNA sequencing of fibroblasts in normal wound healing, breast cancer, ovarian cancer, and melanoma are discussed. These data have revealed differences in expression of established canonical activation marker genes, epigenetic modifications, fibroblast lineages, new gene and proteins of clinical interest for further experimentation, and novel signaling interactions with other cell types that include spatial information.

Keywords: breast cancer; cancer associated fibroblast; melanoma; ovarian cancer; single-cell multiomics; wound healing.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Schematic showing subtypes of wound healing fibroblasts and their location in early and late/completed wound healing, together with markers from scRNA sequencing data and ATAC seq.
FIGURE 2
FIGURE 2
Schematic of CAF populations in ovarian (left) and breast cancer (right) -- summarizing subtypes with highest concordance as well as markers of treatment resistance and survival.
FIGURE 3
FIGURE 3
Schematic summarizing CAFs populations in melanoma -- summarizing subtypes in categories with highest concordance and markers of treatment resistance and survival. The arrow at the top of the figure indicates increasing tumor progression moving from left to right.
See this image and copyright information in PMC

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