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Pancreatic progenitors: From the organ to the plate

Speaker
  • Research Associate, Center for Regenerative Medicine in Barcelona
    Biography
      Meritxell Rovira holds a Bachelor in Biology (2001) from University of Barcelona and a PhD in Health and Life Science (2007) from University Pompeu Fabra. After her PhD she moved to USA in 2008 for her postdoctoral training at Johns Hopkins/School of Medicine to work in Steve D Leach and Mike Parsons laboratories, where she acquired expertise in adult pancreatic progenitors in mouse and zebrafish models. She came back to Barcelona in 2011 as a Marie Curie postdoctoral fellow at Jorge Ferrer laboratory (IDIBAPS) where she gained expertise in the field of epigenetics. After her postdoctoral training, she joined Núria López-Bigas laboratory at IRB as a research associate to stablish and supervise the experimental part of Núria's lab. She joined the CMR[B] in 2017 after being awarded with a Jovenes Investigadores fellowship from the Spanish Ministry.

      Meritxell's main research interest is the study of pancreatic progenitors in zebrafish, mouse and human. Embryonic pancreatic multipotent progenitors and adult pancreatic duct cells express common markers in all animal species studied thus far; suggesting that adult duct cells might be exploited to create a pool of β-cell progenitors. Thus my main research interest is to understand the transcriptional and epigenetic changes that occur between embryonic progenitors and adult cells, as well as the influence of the extrinsic signals from the surrounding mesenchymal cells. This knowledge will allow the identification of the molecular mechanisms that restrict the lineage potential of duct cells and could be used to create a model of β-cell regeneration for the treatment of Type 1 Diabetes.

    Abstract

    Ductal cells share several markers with pancreatic embryonic progenitors, suggesting that ductal cells could be the closest lineage to an adult progenitor in the pancreas, thus their stem-like capacities in vitro have been under intense investigation. A commonly used assay for identifying stem or progenitor cells involves the isolation and culture of candidate cells under specific culture conditions to test their ability to generate colonies/spheres or organoids that can differentiate into multiple cell lineages either in vitro or following transplantation in vivo (Deleyrolle and Reynolds, 2009). Using such strategies, several cell types from the exocrine pancreatic compartment have been shown to acquire stem/progenitor-like properties in vitro (Rovira et al., 2010, Seaberg et al., 2004, Huch et al., 2013, Baeyens et al., 2005).

    These research efforts have demonstrated that ductal/centroacinar cells, from human or mouse origin, can form spheres in suspension culture as well as organoids that under specific growth factor conditions or after kidney capsule engraftment can differentiate into β cells (Rovira et al., 2010, Huch et al., 2013, Boj et al., 2015, Seaberg et al., 2004, Jin et al., 2013, Lee et al., 2013). These organoid cultures represent a useful tool to study pancreas biology in an untransformed system in vitro, from human and mouse pancreatic ducts. This culture system together with new tools for genome editing holds promise for the study of pancreatic diseases and their progression (Huch et al., 2013, Huch and Koo, 2015, Hindley et al., 2016, Broutier et al., 2016).

    Moreover, knowledge gained from studying the acquisition of stem-like/progenitor properties by some terminally differentiated pancreatic cell types in vitro can provide invaluable insight into harnessing these cells for regenerative therapy. Such studies can lead to defining the signaling pathways or growth factors whose activation in vivo is required to generate the proper niche that allow such population to act as dedicated or facultative progenitors.


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