NGDC - GSA for Human

∗This dataset has not yet been registered in the Human Genetic Resource Management Platform of MOST

HRA004376

Title:

Multi-omics analysis reveals the chemoresistance mechanism of proliferating tissue-resident macrophages in PDAC via metabolic adaptation

Release date:

2023-04-17

Description:

We adopted multi-omics strategies, such as single-cell RNA sequencing (scRNA-seq), transcriptomics, multi-immunohistochemistry (mIHC), flow cytometry, and metabolomics to analyze chemo-treated samples from humans and mice to identify the critical macrophage subset for PDAC chemo-resistance. Furthermore, we utilized clinical samples, an orthotopic mouse model, and a transgenic mice model targeting proliferating resident macrophages to verify our findings. We found four major TAM subsets within PDAC, of which proliferating resident macrophage was strongly associated with poor clinical outcomes, and they were able to survive chemotherapy by producing more deoxycytidine (dC) and less deoxycytidine kinase (dCK) to reduce the absorption of gemcitabine. In addition, proliferating rMacrophage could promote fibrosis and immunosuppression in PDAC. Eliminating proliferating rMacrophage in the transgenic mouse model could alleviate the fibrosis and immunosuppression, thus re-sensitizing PDAC to chemotherapy.

Data Accessibility:

Open access

BioProject:

PRJCA013917

Study type:

Disease Study

Disease name:

pancreatic cancer

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