GeniOmics

公开知识文档

Single-cell RNA sequencing and spatial transcriptomics reveal cancer-associated fibroblasts in glioblastoma with protumoral effects.

Cancer-associated fibroblasts (CAFs) were presumed absent in glioblastoma given the lack of brain fibroblasts. Serial trypsinization of glioblastoma specimens yielded cells with CAF morphology and single-cell transcriptomic profiles based on their lack of copy number variations (CNVs) and elevated individual cell CAF probability scores derived from the expression of 9 CAF markers and absence of 5 markers from non-CAF stromal cells sharing features with CAFs. Cells without CNVs and with high CAF probability scores were identified in single-cell RNA-Seq of 12 patient glioblastomas. Pseudotime reconstruction revealed that immature CAFs evolved into subtypes, with mature CAFs expressing actin alpha 2, smooth muscle (ACTA2). Spatial transcriptomics from 16 patient glioblastomas confirmed CAF proximity to mesenchymal glioblastoma stem cells (GSCs), endothelial cells, and M2 macrophages. CAFs were chemotactically attracted to GSCs, and CAFs enriched GSCs. We created a resource of inferred cro

打开平台知识库

Single-cell RNA sequencing and spatial transcriptomics reveal cancer-associated fibroblasts in glioblastoma with protumoral effects.

> 商业许可源文 · EUROPE_PMC · [CC-BY](https://creativecommons.org/licenses/by/)

书目信息

  • 引用：Jain S, Rick JW, Joshi RS, Beniwal A, Spatz J, Gill S, Chang AC, Choudhary N, Nguyen AT, Sudhir S, Chalif EJ, Chen JS, Chandra A, Haddad AF, Wadhwa H, Shah SS, Choi S, Hayes JL, Wang L, Yagnik G, Costello JF, Diaz A, Heiland DH, Aghi MK. (2023). Single-cell RNA sequencing and spatial transcriptomics reveal cancer-associated fibroblasts in glioblastoma with protumoral effects. The Journal of clinical investigation. PMID 36856115 · PMC9974099 · DOI 10.1172/jci147087
  • 证据类型：PRIMARY_RESEARCH
  • 主题：rna-seq、single-cell、spatial-omics
  • 被引次数（采集时）：158
  • 原始记录：[Europe PMC](https://europepmc.org/article/MED/36856115)
  • 来源许可：[CC-BY](https://creativecommons.org/licenses/by/)

    • 作者摘要（按来源许可复用）

    Cancer-associated fibroblasts (CAFs) were presumed absent in glioblastoma given the lack of brain fibroblasts. Serial trypsinization of glioblastoma specimens yielded cells with CAF morphology and single-cell transcriptomic profiles based on their lack of copy number variations (CNVs) and elevated individual cell CAF probability scores derived from the expression of 9 CAF markers and absence of 5 markers from non-CAF stromal cells sharing features with CAFs. Cells without CNVs and with high CAF probability scores were identified in single-cell RNA-Seq of 12 patient glioblastomas. Pseudotime reconstruction revealed that immature CAFs evolved into subtypes, with mature CAFs expressing actin alpha 2, smooth muscle (ACTA2). Spatial transcriptomics from 16 patient glioblastomas confirmed CAF proximity to mesenchymal glioblastoma stem cells (GSCs), endothelial cells, and M2 macrophages. CAFs were chemotactically attracted to GSCs, and CAFs enriched GSCs. We created a resource of inferred crosstalk by mapping expression of receptors to their cognate ligands, identifying PDGF and TGF-β as mediators of GSC effects on CAFs and osteopontin and HGF as mediators of CAF-induced GSC enrichment. CAFs induced M2 macrophage polarization by producing the extra domain A (EDA) fibronectin variant that binds macrophage TLR4. Supplementing GSC-derived xenografts with CAFs enhanced in vivo tumor growth. These findings are among the first to identify glioblastoma CAFs and their GSC interactions, making them an intriguing target.

    合规说明

    本页保存的是来源文献书目信息及其在 CC-BY 许可下公开的作者摘要。除去除来源 HTML 标签和规范化空白外，摘要未作内容改写。本页不代表 GeniOmics 的医学建议；原文版权、署名和许可仍归原权利人，请通过原始记录核对最新版本、更正或撤稿状态。

    Single-cell RNA sequencing and spatial transcriptomics reveal cancer-associated fibroblasts in glioblastoma with protumoral effects. · GeniOmics