Mucin 5ac modulates cancer-associated fibroblast heterogeneity through epigenetic reprogramming of precursor cells.
Kehrberg RJ., Bhyravbhatla N., Alsafwani ZW., Li X., Natarajan G., Khan I.
Prospective Study with a reported sample of 20, published in Am J Physiol Cell Physiol (2025) — summary generated from the PubMed abstract.
Early human evidence such as case series or small samples is exploring possible benefits.
- Level A · Stronger Clinical Evidence
- Level B · Emerging clinical evidence with positive signals
- Level C · Early human research exploring benefits
- Level D · Scientific groundwork from lab and animal studies
- Emerging · Emerging topic under active research
This page is generated from the PubMed record. The Thai description is an automated summary of bibliographic fields and the abstract, not a full translation, and is not medical advice.
- Study type
- Prospective Study
- Journal
- Am J Physiol Cell Physiol (2025)
- Country
- United States
- Reported sample size
- 20
- Source database
- PubMed
- PMID
- 41196138
- PMCID
- PMC13202592
- DOI
- 10.1152/ajpcell.00926.2024
Abstract (original English)
Pancreatic cancer (PC) is characterized by extensive desmoplasia, with heterogeneous cancer-associated fibroblasts (CAFs) as a major component. However, the contribution of distinct precursor cells to CAF heterogeneity remains poorly defined. This study investigated the role of Muc5ac in modulating CAF heterogeneity by maturing precursor cells, including adipose-derived mesenchymal stem cells (AD-MSCs), bone marrow-derived MSCs (BM-MSCs), and pancreatic stellate cells (PSCs), into different CAF subsets. RNA sequencing of precursor cells treated with conditioned media from Muc5ac-proficient or -deficient cancer cells revealed distinct transcriptional profiles. Muc5ac significantly modulated the expression of Dnmts and Tets in AD-MSCs, promoting the acquisition of extracellular matrix production, cytokine signaling, and antigen presentation programs, characteristic of both inflammatory (iCAF) and myofibroblastic (myCAF) CAF phenotypes. In PSCs, Muc5ac increased H3K27 acetylation independent of its interactome, which was validated in autochthonous murine models. Transcriptome analysis demonstrated that AD-MSCs contributed 44.4% to the CAF population, followed by PSCs (31.5%) and BM-MSCs (21.6%). Gene Ontology (GO) and KEGG analyses revealed distinct functional programs for each precursor population contributing to CAF heterogeneity. An age-dependent signature in AD-MSC maturation
What this study does not prove
- • This study does not prove SVF is an approved treatment or a replacement for standard care.
Evidence level
Early human evidence such as case series or small samples is exploring possible benefits.
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