• Uncovering how injury to the pancreas im

    From ScienceDaily@1:317/3 to All on Fri Oct 29 21:30:38 2021
    Uncovering how injury to the pancreas impacts cancer formation

    Date:
    October 29, 2021
    Source:
    Vanderbilt University
    Summary:
    Pioneering research shows that acinar cells in the pancreas form
    new cell types to mitigate injury but are then susceptible to
    cancerous mutations.



    FULL STORY ========================================================================== Pioneering research from scientists at the Vanderbilt University School
    of Medicine Basic Sciences and the Salk Institute for Biological Studies
    shows that acinar cells in the pancreas form new cell types to mitigate
    injury but are then susceptible to cancerous mutations.


    ==========================================================================
    This research, led by Kathy DelGiorno, assistant professor of cell
    and developmental biology at the School of Medicine Basic Sciences,
    Geoffrey Wahl, professor in the Gene Expression Laboratory and holder
    of the Daniel and Martina Lewis Chair at the Salk Institute, and first
    author Zhibo Ma, postdoctoral fellow in the Wahl lab, was published in Gastroenterology on October 22.

    The findings establish a "better understanding of the mechanisms of
    healing in the pancreas and when these processes go awry," DelGiorno
    said. The team used a multidisciplinary approach that combined single-cell
    RNA sequencing, ultrastructural microscopy, genetically engineered models,
    and patient samples to identify the cell types that form in response to pancreatic injury.

    Vanderbilt contributions included computational analysis by Ken Lau,
    associate professor of cell and developmental biology, and various
    microscopy approaches by Dylan Burnette, associate professor of cell and developmental biology, and Rafael Arrojo e Drigo, assistant professor
    of molecular physiology and biophysics.

    From this approach, "we compared our dataset to published datasets
    of gastric injury, oncogene-induced pancreatic neoplasia, and human pancreatitis to identify conserved processes across species and organ
    systems," said DelGiorno.

    According to Wahl, the findings of this paper "support our long-held
    thesis that tissue inflammation causes cells to reprogram to a more
    primitive, developmentally plastic state that under normal circumstances contributes to tissue repair. When subverted by oncogenes like RAS in
    pancreas cancer, it causes one of the most incalcitrant cancers known to medical science." Why It Matters Pancreatic cancer is a major public
    health burden and is slated to become the second-leading cause of cancer-related deaths in the U.S. by the year 2030.

    Currently, the average five-year survival rate for pancreatic cancer is
    only 10 percent, one of the worst of any cancer type. New and innovative treatments are greatly needed to change these outcomes for pancreatic
    cancer patients.

    "Our work captured how these acinar cells change in response to injury
    with incredible resolution. We've been able to identify multiple diverse
    cells generated by the acinar cells and uncover where they came from. Our findings provide a valuable resource to the field of pancreatic cancer
    research for understanding the processes that happen early in pancreas
    injury and tumorigenesis," Ma said.

    "We hope to co-opt and/or target these processes for the benefit of
    patients needing treatment for pancreatitis and cancer," DelGiorno said.

    What's Next? The Vanderbilt team has received a National Institute of
    General Medical Sciences Maximizing Investigators' Research Award to
    follow up on this work.

    "We will be using genetically engineered models to study the lineage trajectories and functional role of the cell types identified in this
    study," DelGiorno said. "We will identify the physiological role of
    these cell types in pancreatic injury, regeneration, and tumorigenesis." ========================================================================== Story Source: Materials provided by Vanderbilt_University. Original
    written by Aaron Conley.

    Note: Content may be edited for style and length.


    ========================================================================== Journal Reference:
    1. 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 C.B. 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. Single-cell transcriptomics reveals a conserved
    metaplasia program in pancreatic injury. Gastroenterology, 2021;
    DOI: 10.1053/j.gastro.2021.10.027 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2021/10/211029103155.htm

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