作者
Zhibo Ma, Nikki K Lytle, Bob Chen, Nidhi Jyotsana, Sammy Weiser Novak, Charles J Cho, Leah Caplan, Olivia Ben-Levy, Abigail C Neininger, Dylan T Burnette, Vincent Q Trinh, Marcus CB Tan, Emilee A Patterson, Rafael Arrojo e Drigo, Rajshekhar R Giraddi, Cynthia Ramos, Anna L Means, Ichiro Matsumoto, Uri Manor, Jason C Mills, James R Goldenring, Ken S Lau, Geoffrey M Wahl, Kathleen E DelGiorno
发表日期
2022/2/1
期刊
Gastroenterology
卷号
162
期号
2
页码范围
604-620. e20
出版商
WB Saunders
简介
Background & Aims
Acinar to ductal metaplasia (ADM) occurs in the pancreas in response to tissue injury and is a potential precursor for adenocarcinoma. The goal of these studies was to define the populations arising from ADM, the associated transcriptional changes, and markers of disease progression.
Methods
Acinar cells were lineage-traced with enhanced yellow fluorescent protein (EYFP) to follow their fate post-injury. Transcripts of more than 13,000 EYFP+ cells were determined using single-cell RNA sequencing (scRNA-seq). Developmental trajectories were generated. Data were compared with gastric metaplasia, KrasG12D-induced neoplasia, and human pancreatitis. Results were confirmed by immunostaining and electron microscopy. KrasG12D was expressed in injury-induced ADM using several inducible Cre drivers. Surgical specimens of chronic pancreatitis from 15 patients were evaluated by …
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