• The origins and ID of pancreatic endocri

    From ScienceDaily@1:317/3 to All on Tue Apr 19 22:30:44 2022
    The origins and ID of pancreatic endocrine cells

    Date:
    April 19, 2022
    Source:
    Universite' de Gene`ve
    Summary:
    Scientists show that endocrine stem cells in the pancreas disappear
    after birth, and detail the genetic identity of the different
    types of pancreatic hormone-producing cells.



    FULL STORY ==========================================================================
    The pancreas is a key metabolic regulator. When pancreatic beta cells
    cease producing enough insulin, blood sugar levels rise dangerously --
    a phenomenon known as hyperglycemia -- thus triggering diabetes. After discovering that other mature pancreatic cells can adapt and partly
    compensate for the lack of insulin, a team from the University of Geneva (UNIGE) demonstrates that the stem cells from which beta cells are
    derived are only present during embryonic development. This discovery
    puts an end to a long-standing controversy about the hypothetical
    existence of adult pancreatic stem cells that would give rise to newly differentiated hormone-producing cells after birth. The scientists
    also succeeded in precisely defining the 'identity card' of pancreatic endocrine cells, which is a promising tool for the production of
    replacement insulin-secreting cells. These results can be read in Cell ReportsandNature Communications.


    ========================================================================== Diabetes is a common metabolic disease. It is characterised by a
    persistent hyperglycemia that occurs when pancreatic cells responsible
    for the production of insulin -- the beta cells -- are destroyed or
    are no longer able to produce this regulatory hormone in sufficient
    quantities. Since 2010, studies performed by the team of Pedro Herrera,
    a professor in the Department of Genetic Medicine and Development and
    in the Diabetes Centre at the UNIGE Faculty of Medicine, as well as at
    the Geneva Institute of Genetics and Genomics (iGE3), reveal that the
    other pancreatic endocrine cells -- namely alpha, delta and gamma cells,
    which produce other hormones useful for the metabolic balance -- can
    "learn" to produce insulin when beta cells are absent or defective. This phenomenon, observed in mice and humans, demonstrates the plasticity of pancreatic cells and paves the way to new therapeutic strategies.

    The short life of pancreatic endocrine stem cells In two recent
    publications, Pedro Herrera's team reports new advances in the knowledge
    of the mechanisms of pancreatic cell formation, and in the gene expression profile defining the identity of each of the different islet endocrine
    cell types. The first research, published and featured in the cover of
    Cell Reports, demonstrates that pancreatic endocrine cells all derive
    from undifferentiated progenitor cells that emerge exclusively during
    embryonic development, but not after birth.

    "Until now, some scientists thought that intra-pancreatic stem cells
    persist throughout life,"explains Pedro Herrera. Marta Perez-Frances,
    a researcher in Pedro Herrera's team and first author of this study,
    adds: "Our work shows that this is not the case. Indeed, all pancreatic hormone-producing cells that emerge after birth originate from the
    division of existing differentiated cells that were generated during
    embryonic and fetal life from undifferentiated progenitor cells."
    To decipher this mechanism, the scientists generated mouse models in
    which the different types of pancreatic endocrine cells were genetically
    tagged with a fluorescent tracer at different developmental stages in
    order to track them down after birth. The cells were traced up to the
    age of ten months, when mice are old.

    A detailed ID card In a second article, published in Nature
    Communications, Pedro Herrera's team focus on the gene expression profile
    of pancreatic endocrine cells. "Precisely defining the 'identity card'
    of these cells now helps us to design a tool aiming at engineering
    cell replacement therapies to treat diabetes. Such therapies could for
    instance consist of in vitro manufacturing of insulin- producing cells,
    or in stimulating pancreatic regeneration by exploiting the plasticity
    of the non-beta cells that we have discovered," explains Le'on van Gurp,
    first author and post-doctoral fellow in the lab of Pedro Herrera.

    The generation of surrogate cells with stable functional identities is
    crucial for the development of cell-based therapies to treat degenerative diseases.

    However, their generation requires reliable tools to accurately assess
    cell identities. To this aim, the researchers performed an extensive meta-analysis of single-cell transcriptomics, i.e. the analysis of
    the genes expressed by individual endocrine cells isolated from human pancreatic islets (these cells are grouped in small "clusters" within
    the pancreas). The identification of robustly expressed gene-sets allow
    the precise definition of the genetic signature of each endocrine cell
    type of the pancreas.

    "Our work has no immediate clinical translation. Yet, by deciphering in
    detail the mechanisms governing the construction of cellular identities,
    it paves the way for developing innovative therapeutic approaches for
    treating diabetes and other pathologies linked to the loss of any given
    cell type,"concludes Pedro Herrera.

    The gene lists that the authors have generated can be downloaded from the Molecular Signatures Database (https://www.gsea-msigdb.org/gsea/msigdb)
    or through the web application scPancMeta (https://rapps.hirnetwork.org/ scPancMeta)

    ========================================================================== Story Source: Materials provided by Universite'_de_Gene`ve. Note:
    Content may be edited for style and length.


    ========================================================================== Journal Reference:
    1. Le'on van Gurp, Leon Fodoulian, Daniel Oropeza, Kenichiro Furuyama,
    Eva
    Bru-Tari, Anh Nguyet Vu, John S. Kaddis, Iva'n Rodri'guez,
    Fabrizio Thorel, Pedro L. Herrera. Generation of human islet cell
    type-specific identity genesets. Nature Communications, 2022; 13
    (1) DOI: 10.1038/ s41467-022-29588-8 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/04/220419092324.htm

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