Article
Agriculture, Dairy & Animal Science
Sara E. Cloft, Zehava Uni, Eric A. Wong
Summary: Mature small intestines have crypts populated by stem cells, which produce replacement cells for maintaining the absorptive villus surface area. The expression of stem cell markers Olfactomedin 4 (Olfm4) and Leucine-rich repeat containing G protein-coupled receptor 5 (Lgr5) differed after hatching, with Olfm4 mRNA increasing and Lgr5 mRNA decreasing. Marker of proliferation Ki67 mRNA decreased post-hatch in the duodenum but was greatest in the ileum. The ontogeny of Olfm4, Lgr5, and Ki67 expressing cells shows that proliferation in the peri-hatch intestine changes from along the entire villi to being restricted within the crypts.
Article
Oncology
Jinnan Xiang, Haoyu Wang, Qianqian Tao, Wenxi Li, Yanfei Huang, Yushuo Zhang, Linan Yang, Shiyi Zhang
Summary: Chemotherapy-induced diarrhea can lead to dehydration, debilitation, infection, and death. However, there are currently no FDA-approved drugs for its treatment. Palbociclib, a CDK4/6 inhibitor, has been shown to regulate the fate of ISCs and protect them from chemotherapy toxicity, leading to accelerated recovery of the gastrointestinal epithelium. It has also been found to enhance the survival of intestinal organoids and ex vivo tissues after chemotherapy. Furthermore, Palbociclib does not reduce the efficacy of cytotoxic chemotherapy in tumor grafts.
JOURNAL OF PATHOLOGY
(2023)
Article
Gastroenterology & Hepatology
Keiko Ishikawa, Shinya Sugimoto, Mayumi Oda, Masayuki Fujii, Sirirat Takahashi, Yuki Ohta, Ai Takano, Kazuhiro Ishimaru, Mami Matano, Kosuke Yoshida, Hikaru Hanyu, Kohta Toshimitsu, Kazuaki Sawada, Mariko Shimokawa, Megumu Saito, Kenta Kawasaki, Ryota Ishii, Koji Taniguchi, Takeshi Imamura, Takanori Kanai, Toshiro Sato
Summary: This study reveals the quiescent nature of human LGR5(+) colonic stem cells and their contribution to post-injury regeneration.
Article
Multidisciplinary Sciences
Laura Sole, Teresa Lobo-Jarne, Daniel Alvarez-Villanueva, Josune Alonso-Maranon, Yolanda Guillen, Marta Guix, Irene Sangrador, Catalina Rozalen, Anna Vert, Antonio Barbachano, Joan Lop, Marta Salido, Beatriz Bellosillo, Raquel Garcia-Romero, Marta Garrido, Jessica Gonzalez, Maria Martinez-Iniesta, Erika Lopez-Arribillaga, Ramon Salazar, Clara Montagut, Ferran Torres, Mar Iglesias, Toni Celia-Terrassa, Alberto Munoz, Alberto Villanueva, Anna Bigas, Lluis Espinosa
Summary: This study reveals that sub-lethal dose of chemotherapy induces a quiescence-like phenotype and a YAP-dependent fetal-like intestinal stem cell state in wild-type p53 colorectal cancers, which is associated with higher metastatic activity and poor prognosis in patients.
NATURE COMMUNICATIONS
(2022)
Article
Gastroenterology & Hepatology
Lei Zhou, Ken H. O. Yu, Tin Lok Wong, Zhao Zhang, Chun Ho Chan, Jane H. C. Loong, Noelia Che, Hua Jian Yu, Kel Vin Tan, Man Tong, Elly S. Ngan, Joshua W. K. Ho, Stephanie Ma
Summary: This study utilized mouse models to investigate the heterogeneity and dynamics of Prom1+ cells in HCC, revealing their CSC-like properties and clonal expansion within tumors. Labelled Prom1+ cells showed increased tumorigenicity in 3D culture and allotransplantation, while depletion of these cells impeded tumor growth. Single-cell RNA sequencing analysis highlighted the heterogeneity of Prom1+ HCC cells and their potential role in disease progression.
Article
Biology
Xiangzhan Zhu, Minglei Yang, Zaijun Lin, Solomon Kibreab Mael, Ya Li, Lili Zhang, Yaqi Kong, Yaodong Zhang, Yuping Ren, Jianhui Li, Zimeng Wang, Ying Zhang, Bo Yang, Tingmei Huang, Fangxia Guan, Zhenlong Li, Robb E. Moses, Lei Li, Bing Wang, Xiaotao Li, Bianhong Zhang
Summary: REG gamma enhances the transcriptional activation of Lgr5 through Wnt and Hippo signal pathways, playing a crucial role in the regeneration of intestinal stem cells.
SCIENCE CHINA-LIFE SCIENCES
(2022)
Article
Gastroenterology & Hepatology
Nobukatsu Horita, Theresa M. Keeley, Elise S. Hibdon, Elizabeth Delgado, Daniel Lafkas, Christian W. Siebel, Linda C. Samuelson
Summary: This study identified specific Notch ligands and Niche cells that regulate stem cell proliferation in the distal mouse stomach. DLL1 was found to be the key Notch ligand that regulates epithelial cell proliferation in the gastric antrum.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Cell Biology
Kristyna Olbertova, Dusan Hrckulak, Vitezslav Kriz, Wojciech Jesionek, Jan Kubovciak, Milan Esner, Vladimir Korinek, Marcela Buchtova
Summary: In this study, the distribution of LGR5-positive cells during craniofacial development was analyzed using Lgr5-EGFP-CreERT2 mice. LGR5 expressing cells were primarily located in the mesenchyme adjacent to the craniofacial epithelial structures undergoing folding. Knockout of the Lgr5 gene led to distinct defects in LGR5-positive areas and abnormal development of craniofacial structures. These findings suggest a novel role of LGR5 in the regulation of morphogenetic processes during the formation of complex epithelial structures in the craniofacial areas.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Mahekta R. Gujar, Yang Gao, Xiang Teng, Wei Yung Ding, Jiaen Lin, Ye Sing Tan, Liang Yuh Chew, Yusuke Toyama, Hongyan Wang
Summary: The ability of stem cells to switch between quiescent and proliferative states is crucial for maintaining tissue homeostasis and regeneration. In this study, researchers found that the microtubule minus-end binding protein Patronin/CAMSAP promotes acentrosomal microtubule growth and quiescent neural stem cell (qNSC) reactivation. This is achieved through its interaction with Arf1 and its involvement in microtubule regulation.
Article
Biochemistry & Molecular Biology
Pilar Baldominos, Alex Barbera-Mourelle, Olga Barreiro, Yu Huang, Andrew Wight, Jae-Won Cho, Xi Zhao, Guillem Estivill, Isam Adam, Xavier Sanchez, Shannon McCarthy, Julien Schaller, Zara Khan, Albert Ruzo, Ricardo Pastorello, Edward T. Richardson, Deborah Dillon, Paula Montero-Llopis, Romualdo Barroso-Sousa, Juliet Forman, Sachet A. Shukla, Sara M. Tolaney, Elizabeth A. Mittendorf, Ulrich H. von Andrian, Kai W. Wucherpfennig, Martin Hemberg, Judith Agudo
Summary: This study discovered that in primary breast cancer, tumor cells that resist T cell attack are quiescent and form clusters with reduced immune infiltration. These quiescent cancer cells show superior tumorigenic capacity and higher expression of chemotherapy resistance and stemness genes. Single-cell RNA sequencing revealed differential phenotypes in infiltrating cells based on their intra-tumor location, and uncovered hypoxia-induced immune-suppressive programs. The findings suggest that eliminating quiescent cancer cells holds the promise to counteract immunotherapy resistance and prevent disease recurrence in TNBC.
Article
Biochemistry & Molecular Biology
Qiannan Deng, Ye Sing Tan, Liang Yuh Chew, Hongyan Wang
Summary: The study revealed that in the protrusion of quiescent NSCs in fruit flies, microtubules are predominantly acentrosomal and oriented plus-end-out towards the tip of the protrusion.
Article
Multidisciplinary Sciences
Kazuhiro Murakami, Yumi Terakado, Kikue Saito, Yoshie Jomen, Haruna Takeda, Masanobu Oshima, Nick Barker
Summary: Safe utilization of the regenerative potential of adult stem cells for clinical applications requires a comprehensive understanding of the regulatory mechanisms. Epithelial organoid cultures accurately mimic in vivo stem cell-driven epithelial renewal, offering a great ex vivo platform for studying key regulatory mechanisms. Through genome-scale CRISPR knockout screening, Alk, Bclaf3, and Prkra were identified as potential regulators of gastric epithelial differentiation and could suppress stemness/proliferation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Francesco Antonica, Lucia Santomaso, Davide Pernici, Linda Petrucci, Giuseppe Aiello, Alessandro Cutarelli, Luciano Conti, Alessandro Romanel, Evelina Miele, Toma Tebaldi, Luca Tiberi
Summary: Quiescent cells in high-grade glioma patients play a significant role in tumor invasiveness, recurrence, and treatment resistance. Targeting and visualizing these cells has been a challenge, but it was found that a population of malignant cells expressing Prominin-1 in a non-proliferating state contribute to tumor infiltration. The use of a DYRK1A/B inhibitor, Harmine, has shown promise in reducing the number of quiescent and infiltrating cancer cells.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Rou Zhao, Baoyu He, Qingli Bie, Jinghe Cao, Haoran Lu, Zhixin Zhang, Jing Liang, Li Wei, Huabao Xiong, Bin Zhang
Summary: This study identifies AQP5 as a specific surface marker for GC-CSCs and reveals its molecular mechanism in promoting tumorigenesis. The study also highlights the importance of targeting both AQP5 and LGR5 as a promising approach for the treatment of gastric cancer.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Hao-Zhe Cao, Wen-Ting Yang, Peng-Sheng Zheng
Summary: The study found that the disulfiram/copper complex has strong cytotoxicity against cervical cancer cells, disrupting the S phase, inhibiting the expression of stemness markers, and reducing the number of cancer stem cell-like LGR5(+) cells, thereby enhancing the anti-tumor effect.
Article
Engineering, Biomedical
Gilles S. van Tienderen, Oskar Rosmark, Ruby Lieshout, Jorke Willemse, Floor de Weijer, Linda Elowsson Rendin, Gunilla Westergren-Thorsson, Michail Doukas, Bas Groot Koerkamp, Martin E. van Royen, Luc J. W. van der Laan, Monique M. A. Verstegen
Summary: Patient-derived tumor organoids were combined with native tumor and liver scaffolds through decellularization to study the interaction between tumor cells and the extracellular matrix (ECM). The use of decellularized scaffolds resulted in a more accurate representation of the in vivo tumor environment and increased chemoresistance. This method also revealed environment-dependent proliferation dynamics and stimulated the production of collagen types.
ACTA BIOMATERIALIA
(2023)
Article
Oncology
Ruby Lieshout, Eline J. C. A. Kamp, Monique M. A. Verstegen, Michail Doukas, Winand N. M. Dinjens, Kubra Koten, Jan N. M. IJzermans, Marco J. Bruno, Maikel P. Peppelenbosch, Luc J. W. van der Laan, Annemarie C. de Vries
Summary: This study reveals that primary sclerosing cholangitis (PSC)-related cholangiocarcinoma (CCA) cells have a higher proliferation rate compared to sporadic CCA cells. The cytokine IL-17A, which is related to inflammation, stimulates the proliferation of CCA cells and may contribute to the high proliferation rate in PSC-CCA. IL-17A represents a potential therapeutic target for (PSC-)CCA.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Medicine, General & Internal
Shaojun Shi, Henk P. Roest, Thierry P. P. van den Bosch, Marcel J. C. Bijvelds, Markus U. Boehnert, Jeroen de Jonge, Sven O. Dekker, Antoine A. F. de Vries, Hugo R. de Jonge, Monique M. A. Verstegen, Luc J. W. van der Laan
Summary: This study successfully replicated ischemic cholangiopathy in vitro using human intrahepatic cholangiocyte organoids stressed by ischemia and subsequent re-oxygenation. The model exhibited similar changes in cell proliferation, epithelial-mesenchymal transition, and cell death processes as observed in patients. The research also identified alpha-1 antitrypsin as a potent inhibitor of ischemia-induced apoptosis and necroptosis.
Article
Materials Science, Biomaterials
Gilles S. van Tienderen, James Conboy, Iain Muntz, Jorke Willemse, Jantine Tieleman, Kathryn Monfils, Ivo J. Schurink, Jeroen A. A. Demmers, Michail Doukas, Gijsje H. Koenderink, Luc J. W. Van der Laan, Monique M. A. Verstegen
Summary: Tumor initiation and progression depend on the interaction between cancer cells and their microenvironment, including the extracellular matrix (ECM). This study extensively characterized the ECM of liver cancer tumors, identifying distinct malignancy-related ECM signatures and divergent mechanical properties. The findings contribute to a better understanding of the alterations to the tumor ECM during liver cancer development.
BIOMATERIALS ADVANCES
(2023)
Article
Gastroenterology & Hepatology
Diego Calvisi, Luke Boulter, Javier Vaquero, Anna Saborowski, Luca M. Fabris, Pedro Rodrigues, Cedric E. Coulouarn, Rui Castro, Oreste Segatto, Chiara Raggi, Luc J. W. van der Laan, Guido Carpino, Benjamin Goeppert, Stephanie J. Roessler, Timothy Kendall, Matthias Evert, Ester W. Gonzalez-Sanchez, Juan Valle, Arndt Vogel, John J. Bridgewater, Mitesh J. Borad, Gregory R. Gores, Lewis Roberts, Jose J. G. B. Marin, Jesper Andersen, Domenico Alvaro, Alejandro M. Forner, Jesus Banales, Vincenzo Cardinale, Rocio I. R. Macias, Silve Vicent, Xin Chen, Chiara Braconi, Monique M. A. Verstegen, Laura Fouassier, Lewis Roberts, Alexander Scheiter, Florin M. Selaru, Katja Evert, Kirsten Utpatel, Laura Broutier, Massimiliano Cadamuro, Meritxell Huch, Robert Goldin, Sergio A. Gradilone, Yoshimasa Saito
Summary: In this Consensus Statement, experts provide recommendations on the criteria for preclinical models of cholangiocarcinoma (CCA) to increase disease understanding and develop novel therapeutic approaches.
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
(2023)
Article
Multidisciplinary Sciences
Yunlong Li, Ruyi Zhang, Yining Wang, Pengfei Li, Yang Li, Harry L. A. Janssen, Robert A. de Man, Maikel P. Peppelenbosch, Xumin Ou, Qiuwei Pan
Summary: Hepatitis E virus (HEV) infection activates NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome by remodeling mature tRNAome in macrophages, leading to pathological inflammation. Inhibition of inflammasome activation abrogates tRNAome remodeling induced by HEV, suggesting a reciprocal interaction between mature tRNAome and NLRP3 inflammasome response. Remodeling of tRNAome improves decoding of codons directing synthesis of leucine and proline, which are major components of IL-1β protein, thereby enhancing inflammasome activation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Oncology
Luc Magre, Monique M. A. Verstegen, Sonja Buschow, Luc J. W. van der Laan, Maikel Peppelenbosch, Jyaysi Desai
Summary: In the past decade, immune system-based treatments have greatly advanced the field of cancer treatment. These therapies have been approved as first-line treatment for certain types of tumors, but their overall clinical efficacy is limited due to tumor heterogeneity and therapy resistance. Predicting patient-specific responses to immunotherapeutic drugs is crucial for personalized treatment and better outcomes.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Letter
Infectious Diseases
Qinyue Zheng, Jaffar A. Al-Taw, Ziad A. Memish, Chunbing Bao, Qiuwei Pan
NEW MICROBES AND NEW INFECTIONS
(2023)
Article
Pharmacology & Pharmacy
Yang Li, Yining Wang, Yunlong Li, Annemarie C. de Vries, Pengfei Li, Maikel P. Peppelenbosch, Qiuwei Pan
Summary: Seasonal coronaviruses are prevalent globally and can cause severe complications in vulnerable populations. Little is known about their pathogenic mechanisms and there are no approved treatments available. This study found that IL-1β levels were elevated in some seasonal coronavirus infected patients, indicating inflammasome activation. Cultured human macrophages supported the lifecycle of three cultivatable seasonal coronaviruses, which activated the NLRP3 inflammasome through TLR4 and NF-κB. Specific inhibitors and clinically used medications attenuated this activation. Combination of antiviral and anti-inflammatory drugs inhibited both the inflammatory response and viral replication. These findings suggest that targeting the TLR4/NF-κB/NLRP3 axis could be a viable therapeutic approach.
ANTIVIRAL RESEARCH
(2023)
Article
Automation & Control Systems
Maarten de Jong, Francesca Cala Campana, Pengfei Li, Qiuwei Pan, Giulia Giordano
Summary: In 2022, the global outbreaks of mpox virus have raised awareness of mpox virus infection and treatment opportunities using drugs cidofovir and tecovirimat, which target different stages of in-host viral proliferation. A new model of in-host viral infection dynamics is proposed to distinguish between the two stages and analyze the effects of the drugs. The model can be simplified to the classical target-cell limited model, and an optimal control problem is solved to schedule optimal combined treatments leveraging the model dynamics.
IEEE CONTROL SYSTEMS LETTERS
(2023)
Article
Microbiology
Jikai Zhang, Chunyang Li, Yao Hou, Dan Liu, Qiudi Li, Zijie Wang, Renxian Tang, Kuiyang Zheng, Hongbo Guo, Wenshi Wang
Summary: miR-26a promotes RIG-I K63 ubiquitination to enhance type I interferon responses by inhibiting USP15 expression, resulting in an active antiviral state against viruses. The activation of type I interferon responses can suppress miR-26a expression to avoid dysregulated signal activation.
MICROBIOLOGY SPECTRUM
(2023)
Meeting Abstract
Immunology
I. J. Schurink, J. Willemse, S. H. Luijmes, F. H. de Goeij, P. C. Groen, E. H. Kucukerbil, M. M. Pascale, S. Shi, W. G. Polak, L. J. van der Laan, J. de Jonge
