한빛사논문
- 조회309
Ki Oh 1, Yun Jae Yoo 1, Luke A Torre-Healy 1, Manisha Rao 2 3, Danielle Fassler 1, Pei Wang 4, Michael Caponegro 5, Mei Gao 6, Joseph Kim 6, Aaron Sasson 7 8, Georgios Georgakis 7 8, Scott Powers 3 8, Richard A Moffitt 9 10 11 *
1Department of Biomedical Informatics, Stony Brook University, Stony Brook, NY, USA.
2Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, USA.
3Department of Pathology, Stony Brook University, Stony Brook, NY, USA.
4Department of Cell Systems & Anatomy, University of Texas Health Science Center, San Antonio, TX, USA.
5Department of Pharmacology, Stony Brook University, Stony Brook, NY, USA.
6Department of Surgery, University of Kentucky and Markey Cancer Center, Lexington, KY, USA.
7Department of Surgery, Stony Brook University, Stony Brook, NY, USA.
8Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY, USA.
9Department of Biomedical Informatics, Stony Brook University, Stony Brook, NY, USA.
10Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA.
11Department of Biomedical Informatics, Emory University, Atlanta, GA, USA.
*Corresponding author: correspondence to Richard A Moffitt
Abstract
Bulk analyses of pancreatic ductal adenocarcinoma (PDAC) samples are complicated by the tumor microenvironment (TME), i.e. signals from fibroblasts, endocrine, exocrine, and immune cells. Despite this, we and others have established tumor and stroma subtypes with prognostic significance. However, understanding of underlying signals driving distinct immune and stromal landscapes is still incomplete. Here we integrate 92 single cell RNA-seq samples from seven independent studies to build a reproducible PDAC atlas with a focus on tumor-TME interdependence. Patients with activated stroma are synonymous with higher myofibroblastic and immunogenic fibroblasts, and furthermore show increased M2-like macrophages and regulatory T-cells. Contrastingly, patients with ‘normal’ stroma show M1-like recruitment, elevated effector and exhausted T-cells. To aid interoperability of future studies, we provide a pretrained cell type classifier and an atlas of subtype-based signaling factors that we also validate in mouse data. Ultimately, this work leverages the heterogeneity among single-cell studies to create a comprehensive view of the orchestra of signaling interactions governing PDAC.
논문정보
- Research article
- 2023년 08월 (BRIC 등록일 2023-09-11)
- 국외 연구진
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