Title

Single-nucleus Transcriptome Profiling of Cancer-associated Fibroblasts in Glioma

Document Type

Article

Publication Date

Summer 2022

Keywords

JGM

JAX Location

In: Student Reports, Summer 2022, The Jackson Laboratory

Abstract

Glioma is responsible for most primary tumor deaths and can often be difficult to treat because of its high heterogeneity. The tumor microenvironment (TME) of glioma is a major contributor to its heterogeneity, and TME fibroblast cells can be recruited by tumor cells and turned into cancer associated fibroblasts (CAFs) which can promote, among else, tumor growth and immune escape. However, fibroblasts in glioma haven’t been studied as extensively as some other glioma TME cells, and they were shown to regulate cancer stemness through paracrine networks1. Here, we used unsupervised clustering on single-nucleus RNA sequencing data to identify fibroblast subpopulations and assessed their gene expression and copy number alteration burden. The original cohort fibroblast cluster was observed to contain two general populations of malignant and non-malignant cells. Withing the non-malignant population we identified two populations of fibroblast cells. They were demonstrated to have high and differential expression for fibroblast marker genes and a low copy number alteration burden, suggesting non-malignancy. The fibroblast populations were then shown to be composed of CAFs and normal associated fibroblasts (NAFs) due to differential expression of CAF and NAF marker genes. Characterizing the CAFs detected to study their interactions with glioma tumor cells could give insight into pathways that can be targeted to alter CAF function.

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