Scholarlink

Introduction <p>Pancreatic ductal adenocarcinoma (PDAC) is characterised by a pronounced desmoplastic reaction, predominantly composed of cancer-associated fibroblasts (CAFs), including myofibroblastic CAFs (myCAFs).</p> Methods <p>We performed a single-cell assay for transposase-accessible chromatin with high-throughput sequencing (scATAC-seq) and single-cell RNA sequencing (scRNA-seq) on pancreas tissues from KPC mice (<i>LSL</i>-<i>Kras</i><sup>G12D/+</sup>; <i>LSL</i>-<i>Trp53</i><sup>R172H/+</sup>; <i>Pdx-1-Cre</i>) to characterise myCAF heterogeneity. A transgelin (<i>Tagln</i>) knockout orthotopic mouse model was used to determine the functional role of Tagln.</p> Results <p>Epigenetic profiling uncovered heterogeneity within the myCAF population, revealing distinct subclusters characterised by specific transcription factor (TF) motifs, such as Srf, Cebpb, Prrx1, and Smad4. We identified three transcriptionally distinct myCAF subtypes, each enriched for unique TF–associated signalling pathways. Among the identified myCAF subtypes, Tagln emerged as a potential functional driver. <i>Tagln</i> knockout mice exhibited significantly reduced PDAC tumour burden compared to wild-type. Analysis of TCGA revealed that high <i>TAGLN</i> expression in PDAC samples was associated with poor survival.</p> Conclusions <p>Our findings highlight the functional heterogeneity of myCAFs and identify TAGLN-expressing myCAFs as critical mediators of tumour progression, providing evidence that targeting stromal TAGLN may represent a promising therapeutic strategy for PDAC.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Transgelin defines pro-tumorigenic cancer-associated fibroblasts in pancreatic cancer

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月16日

查看全文
  • Xingxing Wang,
  • Keiko Shinjo,
  • Kohei Kumegawa,
  • Reo Maruyama,
  • Shinji Mii,
  • Yukihiro Shiraki,
  • Tastunori Nishimura,
  • Yoshiteru Murofushi,
  • Miho Suzuki,
  • Takanobu Kabasawa,
  • Mitsuru Futakuchi,
  • Akinori Kanai,
  • Yutaka Suzuki,
  • Atsushi Enomoto,
  • Yutaka Kondo

摘要

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is characterised by a pronounced desmoplastic reaction, predominantly composed of cancer-associated fibroblasts (CAFs), including myofibroblastic CAFs (myCAFs).

Methods

We performed a single-cell assay for transposase-accessible chromatin with high-throughput sequencing (scATAC-seq) and single-cell RNA sequencing (scRNA-seq) on pancreas tissues from KPC mice (LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx-1-Cre) to characterise myCAF heterogeneity. A transgelin (Tagln) knockout orthotopic mouse model was used to determine the functional role of Tagln.

Results

Epigenetic profiling uncovered heterogeneity within the myCAF population, revealing distinct subclusters characterised by specific transcription factor (TF) motifs, such as Srf, Cebpb, Prrx1, and Smad4. We identified three transcriptionally distinct myCAF subtypes, each enriched for unique TF–associated signalling pathways. Among the identified myCAF subtypes, Tagln emerged as a potential functional driver. Tagln knockout mice exhibited significantly reduced PDAC tumour burden compared to wild-type. Analysis of TCGA revealed that high TAGLN expression in PDAC samples was associated with poor survival.

Conclusions

Our findings highlight the functional heterogeneity of myCAFs and identify TAGLN-expressing myCAFs as critical mediators of tumour progression, providing evidence that targeting stromal TAGLN may represent a promising therapeutic strategy for PDAC.