ArticleCell stem cell2016
Dclk1 Defines Quiescent Pancreatic Progenitors that Promote Injury-Induced Regeneration and Tumorigenesis.
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Article in Cell stem cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers.
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140citing papers in PubMed
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Who cites it
140 citing papers in PubMed, 228 citations in OpenAlex.
- Understanding development and cellular plasticity in the pancreas in health and disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- Evolutionarily Conserved Epigenetic Regulation of Transcriptional Cell States During Vertebrate Pancreatic Tumorigenesis.Cellular and molecular gastroenterology and hepatology · 2026Article
- Molecular dynamics driving phenotypic divergence among KRAS mutants in pancreatic tumorigenesis.Developmental cell · 2026Article
- AI-Powered Deep Visual Proteomics Reveals Critical Molecular Transitions in Pancreatic Cancer Precursors.Cancer discovery · 2026Article
- GATA4 loss promotes mutantbioRxiv : the preprint server for biology · 2026Article
- Review
- The Stathmin 1-lineage Contributes to Acinar Regeneration but Not to Neoplasia Upon Oncogenic Kras Expression.Cellular and molecular gastroenterology and hepatology · 2026Article
- Downregulation of Sod2 increases atypical flat lesions and dysplasia to advance pancreatic ductal adenocarcinoma.Molecular cancer · 2025Article
- Downregulation of Enteroendocrine Genes Predicts Survival in Colon Cancer: A Bioinformatics-Based Analysis.International journal of molecular sciences · 2025Article
- Cell reprogramming in cancer: Interplay of genetic, epigenetic mechanisms, and the tumor microenvironment in carcinogenesis and metastasis.World journal of clinical oncology · 2025Review
- RalGAP complexes control secretion and primary cilia in pancreatic disease.Life science alliance · 2025Article
- Regulatory network analysis of Dclk1 gene expression reveals a tuft cell-ILC2 axis that inhibits pancreatic tumor progression.Cell reports · 2025Article
- Balancing Regeneration and Resistance: Targeting DCLK1 to Mitigate Gastrointestinal Radiation Injury and Oncogenesis.Cancers · 2025Review
- Tuft cells transdifferentiate to neural-like progenitor cells in the progression of pancreatic cancer.Developmental cell · 2025Article
- Identification of mouse and human embryonic pancreatic cells with adult ProcrFrontiers in endocrinology · 2025Article
- Regulatory network analysis ofbioRxiv : the preprint server for biology · 2024Article
- The doublecortin-family kinase ZYG-8DCLK1 regulates microtubule dynamics and motor-driven forces to promote the stability of C. elegans acentrosomal spindles.PLoS genetics · 2024Article
- Tuft cells transdifferentiate to neural-like progenitor cells in the progression of pancreatic cancer.bioRxiv : the preprint server for biology · 2024Article
- Kinome-wide siRNA screen identifies a DCLK2-TBK1 oncogenic signaling axis in clear cell renal cell carcinoma.Molecular cell · 2024Article
- Identification and analysis of pancreatic intraepithelial neoplasia: opportunities and challenges.Frontiers in endocrinology · 2024Review
80 more citing papers are in PubMed but not listed here.
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Authors and funding
29 authors at 7 institutions in 3 countries.
C Benedikt WestphalenDepartment of Internal Medicine III, Hospital of the University of Munich D-81377, Munich, Germany; Department of Digestive and Liver Diseases, Columbia University Medical Center, New York, NY 10032, USA.
Yoshihiro TakemotoDepartment of Digestive and Liver Diseases, Columbia University Medical Center, New York, NY 10032, USA.
Takayuki TanakaDepartment of Digestive and Liver Diseases, Columbia University Medical Center, New York, NY 10032, USA.
Marina MacchiniDepartment of Digestive and Liver Diseases, Columbia University Medical Center, New York, NY 10032, USA; Department of Experimental, Diagnostic and Specialty Medicine, Bologna University, 40128 Bologna, Italy.
Zhengyu JiangDepartment of Digestive and Liver Diseases, Columbia University Medical Center, New York, NY 10032, USA.
Bernhard W RenzDepartment of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Hospital of the University of Munich D-81377, Munich, Germany; Department of Digestive and Liver Diseases, Columbia University Medical Center, New York, NY 10032, USA.
Xiaowei ChenDepartment of Digestive and Liver Diseases, Columbia University Medical Center, New York, NY 10032, USA.
Steffen OrmannsDepartment of Pathology, Hospital of the University of Munich D-81377, Munich, Germany.
Karan NagarDepartment of Digestive and Liver Diseases, Columbia University Medical Center, New York, NY 10032, USA.
Yagnesh TailorDepartment of Digestive and Liver Diseases, Columbia University Medical Center, New York, NY 10032, USA.
Randal MayDepartment of Digestive Diseases and Nutrition, University of Oklahoma, Oklahoma City, OK 73104, USA.
Youngjin ChoDepartment of Pharmacology, Columbia University Medical Center, New York, NY 10032, USA.
Samuel AsfahaDepartment of Digestive and Liver Diseases, Columbia University Medical Center, New York, NY 10032, USA.
Daniel L WorthleyDepartment of Digestive and Liver Diseases, Columbia University Medical Center, New York, NY 10032, USA.
Yoku HayakawaDepartment of Digestive and Liver Diseases, Columbia University Medical Center, New York, NY 10032, USA.
Aleksandra M UrbanskaDepartment of Digestive and Liver Diseases, Columbia University Medical Center, New York, NY 10032, USA.
Michael QuanteDepartment of Internal Medicine II, Klinikum rechts der Isar II, Technische Universität München, D-81675 Munich, Germany.
Maximilian ReichertDepartment of Internal Medicine II, Klinikum rechts der Isar II, Technische Universität München, D-81675 Munich, Germany; Division of Gastroenterology, Department of Medicine, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Joshua BroydeDepartment of Systems Biology, Columbia University Medical Center, New York, NY 10032, USA.
Prem S SubramaniamDepartment of Systems Biology, Columbia University Medical Center, New York, NY 10032, USA.
Helen RemottiDepartment of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA.
Gloria H SuDepartment of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA; Department of Otolaryngology / Head & Neck Surgery, Columbia University Medical Center, New York, NY 10032, USA.
Anil K RustgiDivision of Gastroenterology, Department of Medicine, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Richard A FriedmanDepartment of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA; Department of Biomedical Informatics, Columbia University Medical Center, New York, NY 10032, USA.
Barry HonigDepartment of Pharmacology, Columbia University Medical Center, New York, NY 10032, USA.
Andrea CalifanoDepartment of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA; Department of Otolaryngology / Head & Neck Surgery, Columbia University Medical Center, New York, NY 10032, USA; Department of Biomedical Informatics, Columbia University Medical Center, New York, NY 10032, USA; Department of Systems Biology, Columbia University Medical Center, New York, NY 10032, USA; Department of Biochemistry and Molecular Biophysics, Columbia University Medical Center, New York, NY 10032, USA; Institute for Cancer Genetics, Columbia University, New York, NY 10032, USA; Center for Computational Biology and Bioinformatics (C2B2), Columbia University, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA.
Courtney W HouchenDepartment of Digestive Diseases and Nutrition, University of Oklahoma, Oklahoma City, OK 73104, USA.
Kenneth P OliveDepartment of Digestive and Liver Diseases, Columbia University Medical Center, New York, NY 10032, USA; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA.
Timothy C WangDepartment of Digestive and Liver Diseases, Columbia University Medical Center, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA. Electronic address: tcw21@columbia.edu.
Columbia University Irving Medical Center · USUniversity of Oklahoma Health Sciences Center · USKlinikum rechts der Isar · DELudwig-Maximilians-Universität München · DETechnical University of Munich · DEUniversity of Bologna · ITUniversity of Pennsylvania · US
Funding
Predicting Cancer Cell Response to Endogenous and Exogenous Perturbations at the Single Cell LevelR35CA197745 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ANDREA CALIFANO · 2015 to 2026
$11.5MThe Prrx-1 transcription factor in pancreatic ductal biologyR01DK060694 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI CHANDWANI, ROHIT, RUSTGI, ANIL K · 2002 to 2025
$8.3MSystems Biology of Tumor Progression and Drug ResistanceU01CA168426 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CALIFANO, ANDREA · 2012 to 2016
$6.5MCOMPUTER STUDIES OF PROTEIN STRUCTURE AND FUNCTIONR01GM030518 · NIGMS · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI HONIG, BARRY H · 1985 to 2020
$4.5MMouse Model for Human Pancreatic Ductal AdenocarcinomaR01CA109525 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SU, GLORIA HUEI-TING · 2004 to 2015
$2.6MHigh-performance compute cluster for biomedical computingS10OD012351 · OD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CALIFANO, ANDREA · 2012 to 2012
$2.0MCOMPUTER STUDIES OF PROTEIN STRUCTURE AND FUNCTIONR37GM030518 · NIGMS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI HONIG, BARRY H · 1995 to 2004
$1.5MTraining Program in Computational BiologyT32GM082797 · NIGMS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI HONIG, BARRY H · 2008 to 2015
$1.4MQuiescent Dclk1+ stem cells in the mouse intestineR01DK097016 · NIDDK · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI WANG, TIMOTHY CRAGIN · 2013 to 2015
$950kStorage System for High Performance ComputingS10OD021764 · OD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CALIFANO, ANDREA · 2016 to 2016
$600kCIHRHoward Hughes Medical InstituteNCI NIH HHS R01 CA109525NCI NIH HHS R35 CA197745NCI NIH HHS U01 CA168426NCI NIH HHS U01CA168426NIDDK NIH HHS R01 DK060694NIDDK NIH HHS R01 DK097016NIGMS NIH HHS GM30518NIGMS NIH HHS R01 GM030518NIGMS NIH HHS R37 GM030518NIGMS NIH HHS T32 GM082797NIH HHS S10 OD012351NIH HHS S10 OD021764
Abstract
The existence of adult pancreatic progenitor cells has been debated. While some favor the concept of facultative progenitors involved in homeostasis and repair, neither a location nor markers for such cells have been defined. Using genetic lineage tracing, we show that Doublecortin-like kinase-1 (Dclk1) labels a rare population of long-lived, quiescent pancreatic cells. In vitro, Dclk1+ cells proliferate readily and sustain pancreatic organoid growth. In vivo, Dclk1+ cells are necessary for pancreatic regeneration following injury and chronic inflammation. Accordingly, their loss has detrimental effects after cerulein-induced pancreatitis. Expression of mutant Kras in Dclk1+ cells does not affect their quiescence or longevity. However, experimental pancreatitis converts Kras mutant Dclk1+ cells into potent cancer-initiating cells. As a potential effector of Kras, Dclk1 contributes functionally to the pathogenesis of pancreatic cancer. Taken together, these observations indicate that Dclk1 marks quiescent pancreatic progenitors that are candidates for the origin of pancreatic cancer.
Indexed as
Administration, OralAnimalsCarcinogenesisCarcinoma, Pancreatic DuctalCell ProliferationDoublecortin-Like KinasesMiceOrganoidsPancreatic NeoplasmsPancreatitisProtein Serine-Threonine KinasesTamoxifenDclk1 protein, mouseDoublecortin-Like KinasesProtein Serine-Threonine KinasesTamoxifen
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