Unlimited in vitro expansion of adult bi-potent pancreas progenitors through the Lgr5/R-spondin axis
By Meritxell Huch, P. Bonfanti, S. Boj, Toshiro Sato, Cindy J. M. Loomans, M. van de Wetering, M. Sojoodi, Vivian S. W. Li, Jurian Schuijers, A. Gračanin and 9 more. EMBO Journal, 2013
675 citations recorded by the source corpus.
Lgr5 marks adult stem cells in multiple adult organs and is a receptor for the Wnt‐agonistic R‐spondins (RSPOs). Intestinal, stomach and liver Lgr5+ stem cells grow in 3D cultures to form ever‐expanding organoids, which resemble the tissues of origin. Wnt signalling is inactive and Lgr5 is not expressed under physiological conditions in the adult pancreas. However, we now report that the Wnt pathway is robustly activated upon injury by partial duct ligation (PDL), concomitant with the appearance of Lgr5 expression in regenerating pancreatic ducts. In vitro, duct fragments from mouse pancreas initiate Lgr5 expression in RSPO1‐based cultures, and develop into budding cyst‐like structures (organoids) that expand five‐fold weekly for >40 weeks. Single isolated duct cells can also be cultured into pancreatic organoids, containing Lgr5 stem/progenitor cells that can be clonally expanded. Clonal pancreas organoids can be induced to differentiate into duct as well as endocrine cells upon transplantation, thus proving their bi‐potentiality.
Subfields: Surgery
View Paper: https://www.semanticscholar.org/paper/4e48c3be12693eb9ec026015d7604168edc096f8
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Citations in the corpus
- Organoid Models of Human and Mouse Ductal Pancreatic Cancer (2014, background): “…organoids by modifying approaches we previously pioneered to culture intestinal (Sato et al., 2009), gastric (Barker et al., 2010), colon carcinoma (Sato et al., 2011), hepatic (Huch et al., 2013b), pancreatic (Huch et al., 2013a), and prostatic organoids (Gao et al., 2014; Karthaus et al., 2014).”
- Wnt/ b -Catenin Signaling, Disease, and Emerging Therapeutic Modalities (2017, background): “…many other organs and tissues, including the hair follicle (Jaks et al., 2008), stomach (Barker et al., 2010), pancreas (Huch et al., 2013a), liver (Huch et al., 2013b), kidney (Barker et al., 2012), ovarial epithelium (Ng et al., 2014), inner ear (Chai et al., 2012; Shi et al., 2012), taste buds…”
- Modeling Development and Disease with Organoids. (2016, background): “Clonal pancreas organoids differentiated along ductal and endocrine lineages when grafted Cell 165, June 16, 2016 1591 in vivo in a developing pancreas, indicative of bipotentiality (Huch et al., 2013a).”
- The R-spondin/Lgr5/Rnf43 module: regulator of Wnt signal strength (2014, positive): “…lineage tracing strategy, Lgr5 was subsequently found to mark stem cells in many other organs and tissues, including the stomach (Barker et al. 2010), pancreas (Huch et al. 2013a), liver (Huch et al. 2013b), kidney (Barker et al. 2012), and mammary gland (de Visser et al. 2012; Plaks et al. 2013).”
- Human Primary Liver Cancer -derived Organoid Cultures for disease modelling and drug screening (2017, positive): “79 80 Based on our previous work in mouse liver and pancreas organoid cultures [21, 22], we 81”
- Organoid cultures derived from patients with advanced prostate cancer (2014, positive): “Indeed, others have reported that the growth conditions used here are broadly conducive to growth ofmultiple normal epithelial cell types (Barker et al., 2010; Huch et al., 2013a; Huch et al., 2013b; Sato et al., 2009).”
- Stem Cell Organoid Engineering (2016, positive): “…process can also be reproduced in vitro under specific culture conditions to control self-renewal and differentiation, resulting in self-organized tissue organoids including intestine (Sato et al., 2009), stomach (Barker et al., 2010), liver (Huch et al., 2013), and pancreas (Huch et al., 2013).”
- Functional repair of CFTR by CRISPR/Cas9 in intestinal stem cell organoids of cystic fibrosis patients. (2013, background): “Successful transplantation of Cell clonal organoids derived from single Lgr5+ stem cells into damaged tissue has been demonstrated for mouse colon and liver, making the organoid system a promising tool for adult stem cell/gene therapy (Huch et al., 2013a; Yui et al., 2012).”
- Long-Term Culture of Genome-Stable Bipotent Stem Cells from Adult Human Liver (2015, positive): “Lgr5 , the receptor for the Wnt agonists R-spondins (Carmon et al., 2011; de Lau et al., 2011), marks adult stem cells in these mouse tissues (Barker et al., 2007, 2010; Huch et al., 2013a, 2013b).”