Article
Medicine, Research & Experimental
Anne-Sophie Fischer, Stefanie Muellerke, Alexander Arnold, Julian Heuberger, Hilmar Berger, Manqiang Lin, Hans-Joachim Mollenkopf, Jonas Wizenty, David Horst, Frank Tacke, Michael Sigal
Summary: The stomach corpus epithelium exhibits organized cellular differentiation controlled by RSPO3 during homeostasis and in response to chronic Helicobacter pylori infection, but its absence promotes pit cell differentiation. RSPO3 plays a crucial role in the recovery of corpus glands after injury, but in the context of chronic H. pylori infection, it leads to severe glandular hyperproliferation and the development of premalignant metaplasia.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Biochemistry & Molecular Biology
Oriane Guillermin, Nikolaos Angelis, Clara M. Sidor, Rachel Ridgway, Anna Baulies, Anna Kucharska, Pedro Antas, Melissa R. Rose, Julia Cordero, Owen Sansom, Vivian S. W. Li, Barry J. Thompson
Summary: Wnt signaling induces gradient proliferation of stem/progenitor cells along the intestinal axis, with YAP-TEAD acting as a key downstream effector. YAP regulates the sensitivity of crypt stem cells to apoptosis and cell proliferation during regeneration, and its nuclear localization is influenced by Src family kinase. The interaction between Wnt and Src-YAP signals plays a crucial role in driving intestinal regeneration.
Article
Multidisciplinary Sciences
Elisa Manieri, Guodong Tie, Ermanno Malagola, Davide Seruggia, Shariq Madha, Adrianna Maglieri, Kun Huang, Yuko Fujiwara, Kevin Zhang, Stuart H. Orkin, Timothy C. Wang, Ruiyang He, Neil Mccarthy, Ramesh A. Shivdasani
Summary: PDGFRA-expressing mesenchyme supports intestinal stem cells. The enabling mesenchymal cell populations in stomach epithelia, which have similar dependencies, are unknown. This study used high-resolution imaging, transcriptional profiling, and organoid assays to identify and analyze regional subpopulations of PDGFRA(+) cells in the mouse stomach and their role in epithelial growth and support.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Hyun-Yi Kim, Shujin Li, Dong-Joon Lee, Jin Hoo Park, Takashi Muramatsu, Hidemitsu Harada, Young-Soo Jung, Han-Sung Jung
Summary: A potential cancer stem cell population was identified in ameloblastoma cells, and the activation of Wnt signaling pathway was found to be a promising therapeutic approach to decrease this population.
CELL PROLIFERATION
(2021)
Article
Cell Biology
Laura E. Sanman, Ina W. Chen, Jake M. Bieber, Veronica Steri, Coralie Trentesaux, Byron Hann, Ophir D. Klein, Lani F. Wu, Steven J. Altschuler
Summary: By investigating the responses of intestinal epithelium to different signaling pathways, it was found that modulation of transit-amplifying cell proliferation can change the ratio of differentiated cell types, highlighting the important role of transit-amplifying cells in tuning differentiated cell-type composition.
DEVELOPMENTAL CELL
(2021)
Article
Multidisciplinary Sciences
Carmen Aguilar, Mindaugas Pauzuolis, Malvika Pompaiah, Ehsan Vafadarnejad, Panagiota Arampatzi, Mara Fischer, Dominik Narres, Mastura Neyazi, Ozge Kayisoglu, Thomas Sell, Nils Bluethgen, Markus Morkel, Armin Wiegering, Christoph-Thomas Germer, Stefan Kircher, Andreas Rosenwald, Antoine-Emmanuel Saliba, Sina Bartfeld
Summary: In this study, it was found that Helicobacter pylori prefers to attach to differentiated cells in the pit region of gastric units. Organoid models were used to validate this phenomenon, and it was discovered that differentiated pit cells with high levels of GKN1, GKN2 and PSCA were more susceptible to H. pylori attachment and CagA translocation. It was also found that attachment was unrelated to the expression of MUC5AC or PSCA, but relied on bacterial chemotaxis towards host cell-released urea, which was proportional to the size of the host cell.
NATURE COMMUNICATIONS
(2022)
Review
Cell Biology
Vangelis Bonis, Carla Rossell, Helmuth Gehart
Summary: The single-layered, simple epithelium of the gastrointestinal tract plays a crucial role in nutrient uptake, metabolism coordination, and pathogen defense. Advances in single-cell sequencing, spatio-temporal profiling, and organoid technology have revealed the complex micro-structure of the intestinal epithelium and the mechanisms that maintain it. Recent studies have also explored the distinct structure of the underlying mesenchyme and its crucial interactions with the epithelium for intestinal function and regeneration.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Virology
Ning Yang, Yunhang Zhang, Yuguang Fu, Yang Li, Shanshan Yang, Jianing Chen, Guangliang Liu
Summary: This study investigated the effects of transmissible gastroenteritis virus (TGEV) infection on the small intestine of pigs and its impact on intestinal stem cells (ISCs). The results revealed that TGEV infection activates the Wnt/beta-catenin pathway to promote the self-renewal of ISCs and facilitate intestinal epithelium regeneration.
JOURNAL OF VIROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Shaocong Wang, Yujia Sun, Xiaomai Liu, Yajun Guo, Yongding Huang, Shoutao Zhang, Qingnan Tian
Summary: As a member of TALE family, Meis1 regulates cell proliferation and differentiation during cell fate commitment, but its mechanism remains unclear. The planarian Dugesia japonica, with abundant neoblasts responsible for organ regeneration, provides an ideal model for studying tissue identity determination. Knockdown of DjMeis1 inhibits neoblast differentiation into eye progenitor cells, resulting in a eyeless phenotype with a normal central nervous system. DjMeis1 is also necessary for the activation of Wnt signaling pathway by promoting Djwnt1 expression during posterior regeneration. Silencing of DjMeis1 suppresses Djwnt1 expression and prevents the reconstruction of posterior poles.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Gastroenterology & Hepatology
Emilia J. Orzechowska-Licari, Agnieszka B. Bialkowska, Vincent W. Yang
Summary: This study reveals that upon ionizing radiation-induced injury, intestinal epithelial cells increase SHH secretion, stimulating stromal cells to secrete WNT ligands, which leads to the activation of reserve intestinal stem cells (rISCs) (marked by BMI1) and subsequent epithelial regeneration.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Therese Seidlitz, Bon-Kyoung Koo, Daniel E. Stange
Summary: Gastric cancer is a common and deadly malignancy with late clinical manifestation and poor survival rates. Patient-derived organoids offer new perspectives for translational clinical applications by allowing in-depth analysis of tissue-specific functions, development, and disease.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Fisheries
Shouwen Chen, Yuxin Gong, Shuxin Li, Dahai Yang, Yuanxing Zhang, Qin Liu
Summary: Pyroptosis, an inflammatory form of programmed cell death, plays a critical role in Hydra tissue regeneration by activating the Wnt signaling pathway. This discovery provides new insights into the functional diversification of the gasdermin family.
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
(2023)
Article
Cell & Tissue Engineering
Ji-Hyun Lee, Somi Kim, Seungmin Han, Jimin Min, Brianna Caldwell, Aileen-Diane Bamford, Andreia Sofia Batista Rocha, JinYoung Park, Sieun Lee, Szu-Hsien Sam Wu, Heetak Lee, Juergen Fink, Sandra Pilat-Carotta, Jihoon Kim, Manon Josserand, Reka Szep-Bakonyi, Yohan An, Young Seok Ju, Anna Philpott, Benjamin D. Simons, Daniel E. Stange, Eunyoung Choi, Bon-Kyoung Koo, Jong Kyoung Kim
Summary: This study identified p57 as a molecular switch for maintaining the reserve stem cell state in chief cells of the stomach. p57 expression is constantly maintained in chief cells during homeostasis but rapidly diminishes after injury, leading to robust proliferation. Overexpression of p57 induces a long-term reserve stem cell state accompanied by altered niche requirements and a mature chief cell phenotype. However, constitutive expression of p57 impairs the injury response of chief cells.
Article
Cell Biology
Aaron J. Huebner, Rebecca A. Gorelov, Ruslan Deviatiiarov, Samuel Demharter, Tobias Kull, Ryan M. Walsh, Marty S. Taylor, Simon Steiger, John T. Mullen, Peter V. Kharchenko, Konrad Hochedlinger
Summary: Huebner et al. developed a 2D culture system to study gastric isthmus stem cells and found that Sox2 plays a role in specifying enterochromaffin cells in the stomach. They showed that cell types in the corpus and antrum regions share similar transcriptional states, including the poorly characterized isthmus stem cells. The 2D culture system can be converted into 3D organoids and was used to demonstrate the importance of Sox2 in generating enterochromaffin cells.
NATURE CELL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Kundanika Mukherjee, Suraj Unniappan
Summary: Phoenixin (PNX) is a newly discovered neuropeptide with isoforms of 14 and 20 amino acids, playing a role in reproductive regulation and potentially affecting food intake and energy balance. Research suggests that PNX-20 is produced in the gut of mice and can act directly on gut cells to regulate metabolic hormones.
Article
Oncology
Bang Manh Tran, Dustin James Flanagan, Gregor Ebert, Nadia Warner, Hoanh Tran, Theodora Fifis, Georgios Kastrappis, Christopher Christophi, Marc Pellegrini, Joseph Torresi, Toby James Phesse, Elizabeth Vincan
Review
Biochemistry & Molecular Biology
Sarah Koushyar, Arfon G. Powell, Elizabeth Vincan, Toby J. Phesse
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Gastroenterology & Hepatology
Marianne Lahde, Sarika Heino, Jenny Hogstrom, Seppo Kaijalainen, Andrey Anisimov, Dustin Flanagan, Pauliina Kallio, Veli-Matti Leppanen, Ari Ristimaki, Olli Ritvos, Katherine Wu, Tuomas Tammela, Michael Hodder, Owen J. Sansom, Kari Alitalo
Summary: Expression of RSPO1 in ApcMin/thorn mice increases apoptosis and reduces proliferation and Wnt signaling in adenoma cells, resulting in development of fewer and smaller intestinal tumors and longer mouse survival.
Article
Oncology
John R. P. Knight, Constantinos Alexandrou, George L. Skalka, Nikola Vlahov, Kathryn Pennel, Leah Officer, Ana Teodosio, Georgios Kanellos, David M. Gay, Sebastian May-Wilson, Ewan M. Smith, Arafath K. Najumudeen, Kathryn Gilroy, Rachel A. Ridgway, Dustin J. Flanagan, Rachael C. L. Smith, Laura McDonald, Craig MacKay, Anne Cheasty, Kerri McArthur, Emma Stanway, Joshua D. Leach, Rene Jackstadt, Joseph A. Waldron, Andrew D. Campbell, Georgios Vlachogiannis, Nicola Valeri, Kevin M. Haigis, Nahum Sonenberg, Christopher G. Proud, Neil P. Jones, Martin E. Swarbrick, Heather J. McKinnon, William J. Faller, John Le Quesne, Joanne Edwards, Anne E. Willis, Martin Bushell, Owen J. Sansom
Summary: KRAS-mutant colorectal cancers exhibit resistance to therapeutics, but targeting the mTORC1 and MNK pathways can sensitize them to rapalogs. This approach has shown effectiveness in mouse models and human organoids, offering a potential strategy for patients with elevated c-MYC expression.
Article
Chemistry, Physical
Simon Collett, Joseph Torresi, Linda Earnest Silveira, Vi Khanh Truong, Dale Christiansen, Bang M. Tran, Elizabeth Vincan, Paul A. Ramsland, Aaron Elbourne
Summary: Cell cultures have been successfully used to study hepatitis C virus (HCV) for many years, with recent research suggesting that polarized cell systems are more suitable for studying HCV infection and dynamics.
JOURNAL OF COLLOID AND INTERFACE SCIENCE
(2021)
Article
Multidisciplinary Sciences
Dustin J. Flanagan, Nalle Pentinmikko, Kalle Luopajarvi, Nicky J. Willis, Kathryn Gilroy, Alexander P. Raven, Lynn Mcgarry, Johanna Englund, Anna T. Webb, Sandra Scharaw, Nadia Nasreddin, Michael C. Hodder, Rachel A. Ridgway, Emma Minnee, Nathalie Sphyris, Ella Gilchrist, Arafath K. Najumudeen, Beatrice Romagnolo, Christine Perret, Ann C. Williams, Hans Clevers, Pirjo Nummela, Marianne Lahde, Kari Alitalo, Ville Hietakangas, Ann Hedley, William Clark, Colin Nixon, Kristina Kirschner, E. Yvonne Jones, Ari Ristimaki, Simon J. Leedham, Paul Fish, Jean-Paul Vincent, Pekka Katajisto, Owen J. Sansom
Summary: The tumour suppressor APC is the most commonly mutated gene in colorectal cancer. Loss of Apc in intestinal stem cells drives the formation of adenomas in mice via increased WNT signalling, while reduced secretion of WNT ligands increases the ability of Apc-mutant intestinal stem cells to colonize a crypt. The study found that Apc-mutant cells are enriched for transcripts encoding several secreted WNT antagonists, with Notum being the most highly expressed. These cells actively inhibit the proliferation of surrounding wild-type crypt cells, outcompeting them in the niche and driving their differentiation.
Article
Cell Biology
Michelle P. Clark, Thao Huynh, Shringar Rao, Liana Mackiewicz, Hugh Mason, Shahla Romal, Michael D. Stutz, Sang H. Ahn, Linda Earnest, Vitina Sozzi, Margaret Littlejohn, Bang M. Tran, Norbert Wiedemann, Elizabeth Vincan, Joseph Torresi, Hans J. Netter, Tokameh Mahmoudi, Peter Revill, Marc Pellegrini, Gregor Ebert
Summary: This study demonstrated a clinically viable strategy for potentially eliminating chronic HBV reservoirs in patients by using orally administered drugs that antagonize the function of cellular inhibitor of apoptosis proteins. The research established a reservoir similar to cccDNA in immunocompetent mice using linearized single genome length HBV DNA and confirmed the clinical relevance of the results using primary human liver organoid models.
CELL DEATH & DISEASE
(2021)
Article
Multidisciplinary Sciences
Joshua D. G. Leach, Nikola Vlahov, Petros Tsantoulis, Rachel A. Ridgway, Dustin J. Flanagan, Kathryn Gilroy, Nathalie Sphyris, Ester G. Vazquez, David F. Vincent, William J. Faller, Michael C. Hodder, Alexander Raven, Sigrid Fey, Arafath K. Najumudeen, Douglas Strathdee, Colin Nixon, Mark Hughes, William Clark, Robin Shaw, Sander R. van Hooff, David J. Huels, Jan Paul Medema, Simon T. Barry, Margaret C. Frame, Asier Unciti-Broceta, Simon J. Leedham, Gareth J. Inman, Rene Jackstadt, Barry J. Thompson, Andrew D. Campbell, Sabine Tejpar, Owen J. Sansom
Summary: Right-sided colorectal cancer (rCRC) has a distinct mutational spectrum compared to the left-sided counterpart. Researchers developed a mouse model of rCRC that mirrors human BRAF-mutant rCRC and demonstrated that loss of TGF beta-receptor signaling and inflammation induce the development of colonic tumors with a foetal-like phenotype.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Georgina E. Riddiough, Theodora Fifis, Katrina A. Walsh, Vijayaragavan Muralidharan, Christopher Christophi, Bang M. Tran, Elizabeth Vincan, Marcos V. Perini
Summary: This study investigates the effects of RAS inhibitor captopril on the Wnt/beta-catenin pathway and phenotypic changes associated with tumor progression in the regenerating liver. The results show that RASi induces increased Wnt signaling while downregulating features of EMT, and significantly reduces the expression of Wnt target genes c-myc and cyclin D1.
Article
Biochemistry & Molecular Biology
Bang M. Tran, Samantha L. Grimley, Julie L. McAuley, Abderrahman Hachani, Linda Earnest, Sharon L. Wong, Leon Caly, Julian Druce, Damian F. J. Purcell, David C. Jackson, Mike Catton, Cameron J. Nowell, Laura Leonie, Georgia Deliyannis, Shafagh A. Waters, Joseph Torresi, Elizabeth Vincan
Summary: The urgent need to combat the COVID-19 pandemic has highlighted the necessity for tissue culture models that accurately replicate human tissues and disease. A nasal epithelium culture system has been tested as a model for SARS-CoV-2 infection, demonstrating robust and reproducible infection. This model can mimic key features of human infection and serve as a pre-clinical model without invasive tissue collection.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Sarika Heino, Shentong Fang, Marianne Lahde, Jenny Hogstrom, Sina Nassiri, Andrew Campbell, Dustin Flanagan, Alexander Raven, Michael Hodder, Nadia Nasreddin, Hai-Hui Xue, Mauro Delorenzi, Simon Leedham, Tatiana Petrova, Owen Sansom, Kari Alitalo
Summary: The somatic mutations in APC or CTNNB1 genes disrupt Wnt signaling pathways and contribute to the initiation and progression of colorectal cancer. The study revealed that Lef1 gene expression is crucial in regulating tumor development, and its deletion led to increased tumor initiation, reduced Wnt antagonist expression, and enhanced Myc proto-oncogene expression in Apc-mutant adenomas.
Review
Biochemistry & Molecular Biology
Sarah Koushyar, Valerie S. Meniel, Toby J. Phesse, Helen B. Pearson
Summary: Aberrant activation of the Wnt pathway is closely related to tumor formation, progression, and therapeutic resistance in prostate cancer. Targeting the Wnt pathway for prostate cancer treatment has shown potential efficacy. However, the functional consequences of activating the Wnt pathway during different stages of prostate cancer progression are still unclear. Preclinical research on targeting Wnt signaling in the treatment of prostate cancer is crucial for identifying effective treatment strategies and improving patient care.
Article
Biochemistry & Molecular Biology
Georgina E. Riddiough, Katrina A. Walsh, Theodora Fifis, Georgios Kastrappis, Bang M. Tran, Elizabeth Vincan, Vijayaragavan Muralidharan, Christopher Christophi, Claire L. Gordon, Marcos V. Perini
Summary: This study investigates the potential antitumor effect of renin-angiotensin system inhibition (RASi) in the regenerating liver following partial hepatectomy for colorectal liver metastasis (CRLM). The findings show that RASi treatment reduces tumor burden and alters immune cell composition in the regenerating liver, suggesting that RASi could be explored as an adjunct therapy for patients undergoing partial hepatectomy for CRLM.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Virology
Alexander J. McAuley, Petrus Jansen van Vuren, Muzaffar-Ur-Rehman Mohammed, Faheem, Sarah Goldie, Shane Riddell, Nathan J. Godde, Ian K. Styles, Matthew P. Bruce, Simran Chahal, Stephanie Keating, Kim R. Blasdell, Mary Tachedjian, Carmel M. O'Brien, Nagendrakumar Balasubramanian Singanallur, John Noel Viana, Aditya V. Vashi, Carl M. Kirkpatrick, Christopher A. MacRaild, Rohan M. Shah, Elizabeth Vincan, Eugene Athan, Darren J. Creek, Natalie L. Trevaskis, Sankaranarayanan Murugesan, Anupama Kumar, Seshadri S. Vasan
Summary: Repurposing licenced drugs for use against COVID-19 is a rapid way to develop new therapeutic options, with several existing drugs showing potential anti-SARS-CoV-2 activity in airway models.
Article
Biology
Daniel Routledge, Sally Rogers, Yosuke Ono, Lucy Brunt, Valerie Meniel, Giusy Tornillo, Hassan Ashktorab, Toby J. Phesse, Steffen Scholpp
Summary: The study demonstrates that gastric cancer cells utilize cytonemes to transport Wnt3 protein intercellularly to promote cell proliferation and survival. Additionally, the membrane-bound scaffolding protein Flotillin-2 is identified as a regulator of these cytonemes in gastric cancer.
