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Visualization of stem cell activity in pancreatic cancer expansion by direct lineage tracing with live imaging.

eLife | 2021

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease. Although rigorous efforts identified the presence of 'cancer stem cells (CSCs)' in PDAC and molecular markers for them, stem cell dynamics in vivo have not been clearly demonstrated. Here we focused on Doublecortin-like kinase 1 (Dclk1), known as a CSC marker of PDAC. Using genetic lineage tracing with a dual-recombinase system and live imaging, we showed that Dclk1+ tumor cells continuously provided progeny cells within pancreatic intraepithelial neoplasia, primary and metastatic PDAC, and PDAC-derived spheroids in vivo and in vitro. Furthermore, genes associated with CSC and epithelial mesenchymal transition were enriched in mouse Dclk1+ and human DCLK1-high PDAC cells. Thus, we provided direct functional evidence for the stem cell activity of Dclk1+ cells in vivo, revealing the essential roles of Dclk1+ cells in expansion of pancreatic neoplasia in all progressive stages.

Pubmed ID: 33393460 RIS Download

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This is a list of tools and resources that we have found mentioned in this publication.


DAVID (tool)

RRID:SCR_001881

Bioinformatics resource system including web server and web service for functional annotation and enrichment analyses of gene lists. Consists of comprehensive knowledgebase and set of functional analysis tools. Includes gene centered database integrating heterogeneous gene annotation resources to facilitate high throughput gene functional analysis.

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Gene Set Enrichment Analysis (tool)

RRID:SCR_003199

Software package for interpreting gene expression data. Used for interpretation of a large-scale experiment by identifying pathways and processes.

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Jackson Laboratory (tool)

RRID:SCR_004633

An independent, nonprofit organization focused on mammalian genetics research to advance human health. Their mission is to discover the genetic basis for preventing, treating, and curing human disease, and to enable research for the global biomedical community. Jackson Laboratory breeds and manages colonies of mice as resources for other research institutions and laboratories, along with providing software and techniques. Jackson Lab also conducts genetic research and provides educational material for various educational levels.

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RRID:SCR_008539

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Abcam (tool)

RRID:SCR_012931

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BD Biosciences (tool)

RRID:SCR_013311

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RRID:SCR_013575

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RRID:IMSR_CRL:490

Mus musculus with name Crl:NU(NCr)-Foxn1nu from IMSR.

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CD44 antibody [IM7] (antibody)

RRID:AB_10898986

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CD24 antibody [M1/69] (antibody)

RRID:AB_2291132

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RRID:AB_2090091

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FlowJo (software resource)

RRID:SCR_008520

Software for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.

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ImageJ (software resource)

RRID:SCR_003070

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NOD.Cg-Prkdcscid/J (organism)

RRID:IMSR_JAX:001303

Mus musculus with name NOD.Cg-Prkdcscid/J from IMSR.

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URMC Multiphoton Microscopy Core (service resource)

RRID:SCR_012362

The mission of the URSMD Multiphoton Core Facility is to provide state-of-the-art multiphoton imaging capabilities to further the biomedical and bio-optical research at the URSMD and the University of Rochester with emphasis on intravital imaging and systems physiology. The Multiphoton Core Facility provides access to an Olympus Fluoview 1000 AOM-MPM imaging system and a Spectra-Physics MaiTai HP DeepSee Ti:Sa laser system with dispersion compensation. Further capabilities include engineering applications for opto-electronics and spectroscopy. Initial meeting with the director regarding the design of the experiments begins the process. Imaging will be initially performed by highly skilled staff to make sure all features of software are added for the study, thereafter, the investigator is trained until they are able to operate the microscope independently. Also offered is a blood gas analysis machine and supporting equipment.

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B6;129-Trp53tm1.1Dgk/J (organism)

RRID:IMSR_JAX:017767

Mus musculus with name B6;129-Trp53tm1.1Dgk/J from IMSR.

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