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Single-cell Transcriptomic Analyses of Mouse Pancreatic Endocrine Cells
Published on: September 30, 2018
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Single-Cell Transcriptomics Reveals a Conserved Metaplasia Program in Pancreatic Injury
Zhibo Ma1, Nikki K Lytle1, Bob Chen2
1Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California.
Gastroenterology
|October 25, 2021
Summary
Pancreatic acinar cells transform into metaplasia after injury, forming new cell types and potentially leading to cancer. This process, involving pyloric metaplasia, is conserved in human pancreatitis.
Area of Science:
- Cell biology
- Gastroenterology
- Oncology
Background:
- Acinar to ductal metaplasia (ADM) is a pancreatic response to injury, potentially preceding adenocarcinoma.
- Understanding ADM's cellular origins and molecular changes is crucial for disease progression insights.
Purpose of the Study:
- Define cell populations arising from pancreatic ADM.
- Characterize transcriptional changes during ADM.
- Identify markers for pancreatic disease progression.
Main Methods:
- Lineage tracing of acinar cells using enhanced yellow fluorescent protein (EYFP).
- Single-cell RNA sequencing (scRNA-seq) of over 13,000 EYFP+ cells.
- Comparative analysis with gastric metaplasia, KrasG12D-induced neoplasia, and human pancreatitis samples.
Main Results:
- scRNA-seq identified a mucin/ductal population in ADM resembling gastric pyloric metaplasia.
- Pyloric metaplasia cells can generate tuft cells and enteroendocrine cells (EECs).
- KrasG12D activation in specific ADM populations drives neoplastic transformation and MUC5AC+ cell formation.
Conclusions:
- Chronic injury induces pancreatic acinar cells to undergo pyloric metaplasia, generating progenitor-like populations.
- ADM-derived EEC subtypes are diverse, and KrasG12D drives neoplasia in ADM.
- This metaplasia program is conserved in human pancreatitis, offering insights into early pancreatic disease events.
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