ArticleGastroenterology2022
Single-Cell Transcriptomics Reveals a Conserved Metaplasia Program in Pancreatic Injury.
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Article in Gastroenterology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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77citing papers in PubMed
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77 citing papers in PubMed, 106 citations in OpenAlex.
- The origins and progression of pyloric metaplasia following gastric mucosal injury.Physiological reviews · 2026Review
- Multi-stromal organoid co-culture modelling reveals epithelial-fibroblast heterogeneity in pancreatic cancer and pancreatitis.Nature cell biology · 2026Article
- Evolutionarily Conserved Epigenetic Regulation of Transcriptional Cell States During Vertebrate Pancreatic Tumorigenesis.Cellular and molecular gastroenterology and hepatology · 2026Article
- Multi-omic single nuclei profiling of murine pancreas shows dynamic epigenetic heterogeneity of acinar cells.Cell death and differentiation · 2026Article
- AI-Powered Deep Visual Proteomics Reveals Critical Molecular Transitions in Pancreatic Cancer Precursors.Cancer discovery · 2026Article
- Acinar-ductal metaplasia in pancreatitis and pancreatic ductal adenocarcinoma.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Presence of Tuft Cells Expressing Hematopoietic Prostaglandin D Synthase in Acinar-to-Ductal Metaplasia in Human Obstructive Pancreatitis.Current issues in molecular biology · 2026Article
- Cancer stem cell plasticity in shaping drug resistance landscapes in prostate cancer.Journal of advanced research · 2026Review
- High-quality acinar cell isolation enables single-cell analysis of healthy and injured pancreas.Cell reports methods · 2026Article
- Klf4-Tymp axis promotes inflammation-driven early tumorigenesis by enhancing kras mutation-induced acinar-to-ductal metaplasia through Pi3k/Akt and Mek/Erk pathways.Journal of experimental & clinical cancer research : CR · 2026Article
- Dietary Fat Content Influences PanIN Progression and Pancreatic Cancer Development in Mice.Cancer research communications · 2026Article
- A method for CRISPR/Cas9-induced genetic barcoding and lineage tracing in sheep.Scientific reports · 2026Article
- Article
- Paligenosis: dual potential of mature cell plasticity in regeneration and tumorigenesis.MedScience · 2026Review
- Novel Acinar Metaplastic States Uncovered in Exocrine Pancreas Disease.Cellular and molecular gastroenterology and hepatology · 2026Article
- Protocadherin 20 Is a POU Class 2 Homeobox 3 Target Gene Required for Proper Tuft Cell Microvillus Organization.Cellular and molecular gastroenterology and hepatology · 2026Article
- The Stathmin 1-lineage Contributes to Acinar Regeneration but Not to Neoplasia Upon Oncogenic Kras Expression.Cellular and molecular gastroenterology and hepatology · 2026Article
- Tuft cell-mediated pathogen sensing and inflammation resolution.Biochemical Society transactions · 2025Review
- Mutant GNAS drives a pyloric metaplasia with tumor suppressive glycans in intraductal papillary mucinous neoplasia.Cell reports · 2025Article
- Dietary Fat Content Influences PanIN Progression and Pancreatic Cancer Development in Mice.bioRxiv : the preprint server for biology · 2025Article
17 more citing papers are in PubMed but not listed here.
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Authors and funding
24 authors at 5 institutions in 1 country.
Zhibo MaGene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California.
Nikki K LytleGene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California.
Bob ChenProgram in Chemical and Physical Biology, Vanderbilt University School of Medicine, Nashville, Tennessee; Epithelial Biology Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
Nidhi JyotsanaDepartment of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee.
Sammy Weiser NovakWaitt Advanced Biophotonics Center, Salk Insitute for Biological Studies, La Jolla, California.
Charles J ChoSection of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas.
Leah CaplanDepartment of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee.
Olivia Ben-LevyDepartment of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee.
Abigail C NeiningerDepartment of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee.
Dylan T BurnetteEpithelial Biology Center, Vanderbilt University School of Medicine, Nashville, Tennessee; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee; Vanderbilt Ingram Cancer Center, Nashville, Tennessee.
Vincent Q TrinhDepartment of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.
Marcus C B TanDepartment of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee; Vanderbilt Digestive Disease Research Center, Vanderbilt University Medical Center, Nashville, Tennessee.
Emilee A PattersonDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee.
Rafael Arrojo E DrigoEpithelial Biology Center, Vanderbilt University School of Medicine, Nashville, Tennessee; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee.
Rajshekhar R GiraddiGene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California.
Cynthia RamosGene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California.
Anna L MeansVanderbilt Ingram Cancer Center, Nashville, Tennessee; Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee; Vanderbilt Digestive Disease Research Center, Vanderbilt University Medical Center, Nashville, Tennessee.
Ichiro MatsumotoMonell Chemical Senses Center, Philadelphia, Pennsylvania.
Uri ManorWaitt Advanced Biophotonics Center, Salk Insitute for Biological Studies, La Jolla, California.
Jason C MillsSection of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas.
James R GoldenringEpithelial Biology Center, Vanderbilt University School of Medicine, Nashville, Tennessee; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee; Vanderbilt Ingram Cancer Center, Nashville, Tennessee; Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee; Vanderbilt Digestive Disease Research Center, Vanderbilt University Medical Center, Nashville, Tennessee; Nashville VA Medical Center, Nashville, Tennessee.
Ken S LauEpithelial Biology Center, Vanderbilt University School of Medicine, Nashville, Tennessee; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee; Vanderbilt Ingram Cancer Center, Nashville, Tennessee; Vanderbilt Digestive Disease Research Center, Vanderbilt University Medical Center, Nashville, Tennessee.
Geoffrey M WahlGene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California.
Kathleen E DelGiornoEpithelial Biology Center, Vanderbilt University School of Medicine, Nashville, Tennessee; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee; Vanderbilt Ingram Cancer Center, Nashville, Tennessee; Vanderbilt Digestive Disease Research Center, Vanderbilt University Medical Center, Nashville, Tennessee. Electronic address: kathleen.delgiorno@vanderbilt.edu.
Vanderbilt University · USSalk Institute for Biological Studies · USBaylor College of Medicine · USVanderbilt University Medical Center · USMonell Chemical Senses Center · US
Funding
Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MATTHEW J TYSKA · 1995 to 2026
$172.8MViral Vector Core (VVC)P30CA014195 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI Ye Zheng · 1985 to 2026
$82.8MTranslational Analysis CoreP30DK058404 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 2002 to 2026
$29.9MTissue Analysis & Molecular Imaging CoreP30DK056338 · NIDDK · BAYLOR COLLEGE OF MEDICINE · PI Geoffrey A Preidis · 2001 to 2026
$28.3MVanderbilt-Ingram Cancer Center SPORE in Gastrointestinal CancerP50CA236733 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI STEPHEN W. FESIK · 2019 to 2026
$19.6MTrainingP41GM103712 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FAEDER, JAMES · 2012 to 2021
$16.3MTRAINING IN THE IMMUNOBIOLOGY AND MOLECULAR CELL BIOLOGY OF CANCERT32CA009547 · NCI · WASHINGTON UNIVERSITY · PI ROBERT DAVID SCHREIBER · 1986 to 2026
$12.1MSalk Institute Cancer Training GrantT32CA009370 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI Diana Clare Hargreaves, Jan Karlseder · 1986 to 2026
$8.6MCombining single cell approaches and a developmental perspective to discover stem cell control circuits and the cellular and molecular bases of cancer heterogeneityR35CA197687 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI WAHL, GEOFFREY MYLES · 2015 to 2021
$7.8MIntegrated Biological Systems Training in OncologyT32CA119925 · NCI · VANDERBILT UNIVERSITY · PI Vivian Gama, William Patrick Tansey · 2008 to 2026
$7.6MREGULATION OF ATROPHY-INDUCED PROGENITOR CELLS IN THE GASTRIC CORPUSR01DK094989 · NIDDK · WASHINGTON UNIVERSITY · PI Jason C Mills · 2012 to 2026
$6.1MInduction and Evolution of Metaplasia in the StomachR01DK101332 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Eunyoung Choi, James Richard Goldenring · 2014 to 2026
$5.9MBLRD VA I01 BX000930Cancer Research UK 27145NCI NIH HHS P30 CA014195NCI NIH HHS P30 CA068485NCI NIH HHS P50 CA236733NCI NIH HHS R01 CA239645NCI NIH HHS R01 CA246208NCI NIH HHS R35 CA197687NCI NIH HHS T32 CA009370NCI NIH HHS T32 CA009547NCI NIH HHS T32 CA119925NCI NIH HHS U01 CA215798NIDDK NIH HHS P30 DK056338NIDDK NIH HHS P30 DK058404NIDDK NIH HHS R01 DK094989NIDDK NIH HHS R01 DK101332NIDDK NIH HHS R01 DK103831NIDDK NIH HHS R01 DK105129NIDDK NIH HHS R01 DK110406NIDDK NIH HHS R03 DK127484NIDDK NIH HHS R21 DK111369NIDDK NIH HHS U01 DK120447NIGMS NIH HHS P41 GM103712NIGMS NIH HHS R35 GM142709NLM NIH HHS T32 LM012412
Abstract
BACKGROUND &
aimsAcinar 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.
methodsAcinar 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, Kras
resultsscRNA-seq of ADM revealed emergence of a mucin/ductal population resembling gastric pyloric metaplasia. Lineage trajectories suggest that some pyloric metaplasia cells can generate tuft and enteroendocrine cells (EECs). Comparison with Kras
conclusionsUnder conditions of chronic injury, acinar cells undergo a pyloric-type metaplasia to mucinous progenitor-like populations, which seed disparate tuft cell and EEC lineages. ADM-derived EEC subtypes are diverse. Kras
Indexed as
Acinar CellsCarcinoma, Pancreatic DuctalCell PlasticityEnteroendocrine CellsGene Expression ProfilingHumansMetaplasiaMucin 5ACPancreasPancreatic DuctsPancreatic NeoplasmsPancreatitisProto-Oncogene Proteins p21(ras)Single-Cell AnalysisKRAS protein, humanMUC5AC protein, humanMucin 5ACProto-Oncogene Proteins p21(ras)ADMEnteroendocrine CellsPaligenosisPlasticityTuft Cells
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