Single Cell Analysis of Cultivated Fibroblasts from Chronic Pancreatitis and Pancreatic Cancer Patients

Bibliographic Details
Title: Single Cell Analysis of Cultivated Fibroblasts from Chronic Pancreatitis and Pancreatic Cancer Patients
Authors: Yoshiaki Sunami, Yijun Chen, Bogusz Trojanowicz, Matthias Sommerer, Monika Hämmerle, Roland Eils, Jörg Kleeff
Source: Cells, Vol 11, Iss 16, p 2583 (2022)
Publisher Information: MDPI AG, 2022.
Publication Year: 2022
Collection: LCC:Cytology
Subject Terms: cancer-associated fibroblasts, pancreatic cancer, chronic pancreatitis, single-cell RNA sequencing, cellular plasticity, Cytology, QH573-671
More Details: Cancer-associated fibroblasts (CAFs) play a major role in the progression and drug resistance of pancreatic cancer. Recent studies suggest that CAFs exhibit functional heterogeneity and distinct transcriptomic signatures in pancreatic cancer. Pancreatic fibroblasts also form an integral component in pancreatic diseases such as chronic pancreatitis named disease-associated fibroblasts (DAFs). However, intra-tumoral heterogeneity of CAFs in pancreatic cancer patients and their pivotal role in cancer-related mechanisms have not been fully elucidated. Further, it has not been elucidated whether CAF subtypes identified in pancreatic cancer also exist in chronic pancreatitis. In this study, we used primary isolated fibroblasts from pancreatic cancer and chronic pancreatitis patients using the outgrowth method. Single-cell RNA sequencing (scRNA-seq) was performed, and bioinformatics analysis identified highly variable genes, including factors associated with overall survival of pancreatic cancer patients. The majority of highly variable genes are involved in the cell cycle. Instead of previously classified myofibroblastic (myCAFs), inflammatory (iCAFs), and antigen-presenting (ap) CAFs, we identified a myCAFs-like subtype in all cases. Most interestingly, after cell cycle regression, we observed 135 highly variable genes commonly identified in chronic pancreatitis and pancreatic cancer patients. This study is the first to conduct scRNAseq and bioinformatics analyses to compare CAFs/DAFs from both chronic pancreatitis and pancreatic cancer patients. Further studies are required to select and identify stromal factors in DAFs from chronic pancreatitis cases, which are commonly expressed also in CAFs potentially contributing to pancreatic cancer development.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2073-4409
Relation: https://www.mdpi.com/2073-4409/11/16/2583; https://doaj.org/toc/2073-4409
DOI: 10.3390/cells11162583
Access URL: https://doaj.org/article/de0406e1e63343808aeb13daec24bb8c
Accession Number: edsdoj.0406e1e63343808aeb13daec24bb8c
Database: Directory of Open Access Journals
More Details
ISSN:20734409
DOI:10.3390/cells11162583
Published in:Cells
Language:English