Article
Immunology
Govindarajan Thangavelu, Gabriela Andrejeva, Sara Bolivar-Wagers, Sujeong Jin, Michael C. Zaiken, Michael Loschi, Ethan G. Aguilar, Scott N. Furlan, Chrysothemis C. Brown, Yu-Chi Lee, Cameron McDonald Hyman, Colby J. Feser, Angela Panoskaltsis-Mortari, Keli L. Hippen, Kelli P. MacDonald, William J. Murphy, Ivan Maillard, Geoffrey R. Hill, David H. Munn, Robert Zeiser, Leslie S. Kean, Jeffrey C. Rathmell, Hongbo Chi, Randolph J. Noelle, Bruce R. Blazar
Summary: This study investigated how RA receptor signaling in Tregs influences their function and stability in vivo. The results indicate that RA signaling acts as a rheostat to balance Treg function in inflammatory and noninflammatory conditions.
CELLULAR & MOLECULAR IMMUNOLOGY
(2022)
Article
Cell Biology
Justine Creff, Ada Nowosad, Anne Prel, Anne Pizzoccaro, Marion Aguirrebengoa, Nicolas Duquesnes, Caroline Callot, Thomas Jungas, Christine Dozier, Arnaud Besson
Summary: p57Kip2 is a cyclin/CDK inhibitor that regulates intestinal stem cell (ISC) fate and proliferation in a CDK-independent manner. In the absence of p57, there is increased proliferation of intestinal crypts and amplification of transit-amplifying cells and Hopx+ ISCs. RNA sequencing analyses reveal significant gene expression changes in Hopx+ ISCs upon p57 depletion. Furthermore, p57 binds to and inhibits the activity of Ascl2, a transcription factor critical for ISC specification and maintenance, by recruiting a corepressor complex. Hence, p57 plays a key role in maintaining Hopx+ ISC quiescence and repressing the ISC phenotype by inhibiting Ascl2 in a CDK-independent manner during intestinal development.
Article
Immunology
Suzanne H. Hodge, Maria Z. Krauss, Irem Kaymak, James I. King, Andrew J. M. Howden, Gordana Panic, Richard K. Grencis, Jonathan R. Swann, Linda V. Sinclair, Matthew R. Hepworth
Summary: ILC2 are tissue-resident lymphocytes that respond rapidly to damage and infection at mucosal barrier sites. They are sensitive to cues from the diet and invading pathogens, and also to perturbations in nutrient availability. Amino acid availability has been identified as a nutritional cue in regulating ILC2 responses.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Julie Melendez, Daniel Sieiro, David Salgado, Valerie Morin, Marie-Julie Dejardin, Chan Zhou, Alan C. Mullen, Christophe Marcelle
Summary: Fusion of myoblasts is essential for muscle development and repair, with TGF-beta signaling regulating the pace of fusion through a receptor complementation mechanism and endocytic degradation of activated receptors.
NATURE COMMUNICATIONS
(2021)
Article
Cell & Tissue Engineering
Lucia Cordero-Espinoza, Anna M. Dowbaj, Timo N. Kohler, Bernhard Strauss, Olga Sarlidou, German Belenguer, Clare Pacini, Nuno P. Martins, Ross Dobie, John R. Wilson-Kanamori, Richard Butler, Nicole Prior, Palle Serup, Florian Jug, Neil C. Henderson, Florian Hollfelder, Meritxell Huch
Summary: This study demonstrates that a subpopulation of mouse periportal mesenchymal cells in organoid co-cultures exert dual control on epithelial proliferation, mediated by Notch signaling. Proliferation of ductal cells is influenced by the number of direct mesenchymal cell contacts, highlighting the critical role of cell-cell contacts in regulating cellular behaviors during regeneration.
Article
Pharmacology & Pharmacy
Sitang Ge, Yating Yang, Lugen Zuo, Xue Song, Hexin Wen, Zhijun Geng, Yifan He, Zilong Xu, Huatao Wu, Mengdi Shen, Yuanyuan Ge, Xuejun Sun
Summary: This study investigated the effects of Sotetsuflavone (SF) on CD-like spontaneous colitis. The results showed that SF significantly improved colitis and protected intestinal barrier function in the CD model. SF also suppressed M1 macrophage-induced inflammatory responses via JNK and p38 signaling. SF may have therapeutic potential for CD treatment.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ines Elia, Giulia Realini, Vittoria Di Mauro, Sara Borghi, Laura Bottoni, Salvatore Tornambe, Libero Vitiello, Stephen J. Weiss, Mario Chiariello, Annalaura Tamburrini, Salvatore Oliviero, Francesco Neri, Maurizio Orlandini, Federico Galvagni
Summary: This study reveals that SNAI1 is upregulated during early muscle regeneration and acts as a direct repressor of ER stress and Fgf21 expression. The findings provide insights into the regulatory mechanism of myogenic differentiation and the maintenance of undifferentiated state in myoblasts.
Article
Biochemistry & Molecular Biology
Chong Dai, Adriana Reyes-Ordonez, Jae-Sung You, Jie Chen
Summary: Aminoacyl-tRNA synthetases play essential roles in protein synthesis, with some also exhibiting non-translational functions. Threonyl-tRNA synthetase (ThrRS) has been found to negatively regulate myoblast differentiation through a non-catalytic mechanism involving new domains UNE-T and TGS. ThrRS interacts with Axin1, inhibiting JNK signaling and affecting skeletal myogenesis through the MEKK4-MKK4-JNK pathway.
Article
Gastroenterology & Hepatology
Christine Jones, Mariano Avino, Veronique Giroux, Francois Boudreau
Summary: Transcriptomic analysis revealed the crucial role of HNF4 alpha in supporting the growth and survival of jejunal enteroids, as well as its autonomous function in Wnt3 transcriptional regulation and Paneth cell differentiation.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Cell Biology
Ildiko M. L. Somorjai, Matthias T. Ehebauer, Hector Escriva, Jordi Garcia-Fernandez
Summary: The study demonstrates that pharmacological inhibition of JNK signaling in cephalochordate embryos results in morphological abnormalities such as notochord elongation defects, cell delamination, and altered gene expression. This suggests a conserved role of JNK signaling in regulating cellular behavior and tissue differentiation during cephalochordate morphogenesis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Zhen Dong, Chunyi Li, Dawn Coates
Summary: The growing deer antler contains a stem cell niche that drives bone regeneration at a rapid rate. PTN is a highly expressed growth factor in the antler stem cell tissues, with potential interactions with receptors such as PTPRZ and ALK. In vitro studies show that PTN does not induce differentiation or proliferation in antler stem cells, but rather maintains their stem cell status.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Oncology
Amy J. Tibbo, Andrew Hartley, Richa Vasan, Robin Shaw, Laura Galbraith, Ernest Mui, Hing Y. Leung, Imran Ahmad
Summary: The study found that the MBTPS2 gene alteration is associated with metastatic prostate cancer, and it is involved in the development of prostate cancer through its regulation of fatty acid and cholesterol metabolism.
BRITISH JOURNAL OF CANCER
(2023)
Article
Materials Science, Multidisciplinary
Chiara Pizzolitto, Francesca Scognamiglio, Giovanna Baldini, Roberta Bortul, Gianluca Turco, Ivan Donati, Vanessa Nicolin, Eleonora Marsich
Summary: Chondrocyte-based aggregates were formed by culturing cells on a polymeric coating of a lactose-modified chitosan (CTL). The formation of these aggregates was mainly through cell aggregation rather than proliferation, resulting in structures with an irregular morphology up to 1 mm in size. The lactose-modified chitosan (CTL) acted as a temporary matrix for chondrocyte aggregation during the formation of chondro-aggregates, allowing for innovative therapeutic approaches in cartilage regeneration without the need for a scaffold.
ACS APPLIED POLYMER MATERIALS
(2023)
Review
Medicine, General & Internal
Jing Niu, Yanli Liu, Junjun Wang, Hui Wang, Ying Zhao, Min Zhang
Summary: The degeneration of articular cartilage tissue is a common cause of articular cartilage diseases, such as osteoarthritis. Traditional treatments and chondrocyte self-renewal have limitations in addressing this issue. Thrombospondin-2 has been shown to play an important role in cartilage regeneration, protecting cartilage from damage caused by inflammation or trauma, and activating different intracellular signaling pathways to aid in the regenerative repair of cartilage. These findings provide new insights for cartilage repair in clinical settings.
Article
Developmental Biology
Tetsuya Bando, Misa Okumura, Yuki Bando, Marou Hagiwara, Yoshimasa Hamada, Yoshiyasu Ishimaru, Taro Mito, Eri Kawaguchi, Takeshi Inoue, Kiyokazu Agata, Sumihare Noji, Hideyo Ohuchi
Summary: The study investigates the function of Toll-related molecules in leg regeneration of the two-spotted cricket Gryllus bimaculatus, suggesting that the Spz-Toll-related signaling in plasmatocytes promotes leg regeneration through blastema cell proliferation.
Article
Genetics & Heredity
Shivohum Bahuguna, Magda Atilano, Marcus Glittenberg, Dohun Lee, Srishti Arora, Lihui Wang, Jun Zhou, Siamak P. Redhai, Michael P. Boutros, Petros P. Ligoxygakis
Summary: The immune system of fruit flies recognizes gut bacteria and activates a metabolic pathway to regulate lipid breakdown, which is important for the retention of intestinal bacteria. The TOR pathway inhibits lipid breakdown in fly mutants with reduced immune recognition, leading to increased gut fat accumulation. Blocking the TOR pathway restores both lipid levels and the density of gut bacteria to normal levels.
Article
Biology
Giulia Ambrosi, Oksana Voloshanenko, Antonia F. Eckert, Dominique Kranz, G. Ulrich Nienhaus, Michael Boutros
Summary: Wnt signaling is important in various biological processes, and mutations in beta-catenin can activate this signaling pathway. In this study, fluorescently tagged alleles of wild-type and mutant beta-catenin were engineered and analyzed to understand their properties. The results revealed distinct biophysical properties between the two alleles, and the wild-type allele could be manipulated to mimic the properties of the mutant allele through specific treatments.
Article
Biology
Christopher J. Neufeldt, Berati Cerikan, Mirko Cortese, Jamie Frankish, Ji-Young Lee, Agnieszka Plociennikowska, Florian Heigwer, Vibhu Prasad, Sebastian Joecks, Sandy S. Burkart, David Y. Zander, Baskaran Subramanian, Rayomand Gimi, Seetharamaiyer Padmanabhan, Radhakrishnan Iyer, Mathieu Gendarme, Bachir El Debs, Niels Halama, Uta Merle, Michael Boutros, Marco Binder, Ralf Bartenschlager
Summary: SARS-CoV-2 infection can lead to severe symptoms and long-lasting lung damage or death. This is often associated with high levels of pro-inflammatory cytokines and low antiviral responses. A specific activation of NF-kappa B and block of IRF3 nuclear translocation were observed in infected cells. The inflammatory response is mediated by cGAS-STING activation and can be attenuated through STING-targeting drugs.
COMMUNICATIONS BIOLOGY
(2022)
Article
Oncology
Antonio Sorrentino, Ayse Nur Menevse, Tillmann Michels, Valentina Volpin, Franziska Christine Durst, Julian Sax, Maria Xydia, Abir Hussein, Slava Stamova, Steffen Spoerl, Nicole Heuschneider, Jasmin Muehlbauer, Katharina Marlene Jeltsch, Anchana Rathinasamy, Melanie Werner-Klein, Marco Breinig, Damian Mikietyn, Christian Kohler, Isabel Poschke, Sabrina Purr, Olivia Reidell, Catarina Martins Freire, Rienk Offringa, Claudia Gebhard, Rainer Spang, Michael Rehli, Michael Boutros, Christian Schmidl, Nisit Khandelwal, Philipp Beckhove
Summary: This study reveals a molecular mechanism that protects tumor cells from cytotoxic T-cell attack and demonstrates the feasibility of pharmacological inhibition of this pathway.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
A. Echle, N. Ghaffari Laleh, P. Quirke, H. Grabsch, H. S. Muti, O. L. Saldanha, S. F. Brockmoeller, P. A. van den Brandt, G. G. A. Hutchins, S. D. Richman, K. Horisberger, C. Galata, M. P. Ebert, M. Eckardt, M. Boutros, D. Horst, C. Reissfelder, E. Alwers, T. J. Brinker, R. Langer, J. C. A. Jenniskens, K. Offermans, W. Mueller, R. Gray, S. B. Gruber, J. K. Greenson, G. Rennert, J. D. Bonner, D. Schmolze, J. Chang-Claude, H. Brenner, C. Trautwein, P. Boor, D. Jaeger, N. T. Gaisa, M. Hoffmeister, N. P. West, J. N. Kather
Summary: This study developed an AI-based system to identify microsatellite instability/mismatch repair deficiency in colorectal cancer, achieving high accuracy. The system can be used to rule out MSI/dMMR, reducing the cost and time for molecular profiling.
Article
Oncology
Leonhard Valentin Bamberg, Florian Heigwer, Anna Maxi Wandmacher, Ambika Singh, Johannes Betge, Niklas Rindtorff, Johannes Werner, Julia Josten, Olga Valerievna Skabkina, Isabel Hinsenkamp, Gerrit Erdmann, Christoph Roecken, Matthias P. Ebert, Elke Burgermeister, Tianzuo Zhan, Michael Boutros
Summary: Epigenetic dysregulation plays an important role in colorectal cancer (CRC), and combining histone deacetylase (HDAC) inhibitors with Euchromatic Histone Lysine N-Methyltransferases 1 and 2 (EHMT1/2) inhibitors has shown promising results in reducing CRC growth. Low expression of EHMT2 protein is associated with advanced CRC and poor clinical outcomes. Cotargeting HDAC and EHMT1/2 synergistically reduces proliferation of CRC cell lines through mechanisms such as cell cycle arrest and modulation of autophagy. This combination therapy strategy also decreases tumor viability in advanced models of CRC.
INTERNATIONAL JOURNAL OF CANCER
(2022)
Article
Biochemistry & Molecular Biology
Katharina Imkeller, Giulia Ambrosi, Nancy Klemm, Ainara Claveras Cabezudo, Luisa Henkel, Wolfgang Huber, Michael Boutros
Summary: Wnt pathways regulate tissue homeostasis and their dysfunction is associated with cancer development. This study integrates whole-genome CRISPR/Cas9 screens with multi-omic data to identify functional subtypes of cancer. By engineering cells to hyperactivate Wnt signaling, the authors demonstrate that the resulting cells have an unfavorable metabolic equilibrium compared to naturally occurring Wnt hyperactivation. This study expands our understanding of oncogenic signaling modulation in tumorigenesis.
MOLECULAR SYSTEMS BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Antonia Schubert, Oksana Voloshanenko, Franziska Ragaller, Philipp Gmach, Dominique Kranz, Christian Scheeder, Thilo Miersch, Matthias Schulz, Lorenz Truemper, Claudia Binder, Marko Lampe, Ulrike Engel, Michael Boutros
Summary: Dishevelled proteins play a crucial role in Wnt signaling pathways, and their formation of supramolecular condensates is coordinated dynamically and dependent on cellular state and Wnt signaling levels.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Anna Mendaluk, Emmanuel Caussinus, Michael Boutros, Christian F. Lehner
Summary: A change in ambient temperature affects cellular processes non-uniformly, with enzymes being more sensitive than diffusion. The molecular-level effects of temperature variation on cells are still poorly understood. A genome-wide RNA interference screen identified genes with physiological significance at different temperatures. Validation experiments confirmed the importance of the gene ballchen at lower temperatures.
Review
Developmental Biology
Lucie Wolf, Michael Boutros
Summary: Intercellular communication by Wnt proteins is crucial for development, tissue homeostasis, and disease. The secretion of Wnt proteins depends on Evi/Wntless and Porcupine, which are transmembrane proteins. This review summarizes the transportation of Wnt proteins from the ER to the plasma membrane, the role of SNX3-retromer in this process, the regulation of Wnt secretion, and the importance of Wnt secretion in organ development and cancer.
Review
Biochemistry & Molecular Biology
Johannes Werner, Kim E. Boonekamp, Tianzuo Zhan, Michael Boutros
Summary: Wnt ligands are secreted signaling proteins with a wide range of biological effects. Dysregulation of Wnt signaling is associated with cancer, and genetic alterations result in pathway hyperactivation. Recent research focuses on the interaction of Wnt signaling with tumor micro-environment. The review outlines the function of Wnt ligands in different tumors and their impact on key phenotypes, as well as approaches to target them in cancer therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Michael Baumann, Julio Celis, Ulrik Ringborg, Manuel Heitor, Anton Berns, Tit Albreht, Jeliazko Arabadjiev, Michael Boutros, Mario Brandenburg, Helena Canhao, Fatima Carneiro, Christine Chomienne, Francesco De Lorenzo, Alexander M. M. Eggermont, Angel Font, Elena Garralda, Margarida Goulart, Rui Henrique, Mark Lawler, Lena Maier-Hein, Francoise Meunier, Simon Oberst, Pedro Oliveira, Maria Papatriantafyllou, Joachim Schuez, Eric Solary, Alfonso Valencia, Rosalia Vargas, Elisabete Weiderpass, Nils Wilking
Summary: European cancer research stakeholders gathered in Heidelberg, Germany, for the 5(th) Gago conference on European Cancer Policy in October 2022. The meeting focused on the current state of cancer research and care policy in Europe, identifying gaps in existing programs and proposing priorities for the future through the Heidelberg Manifesto for cancer research. The discussions in the meeting covered various aspects of cancer research, including infrastructure, digitalization, and collaboration, with an emphasis on implementation and sustainability.
MOLECULAR ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Sara Kassel, Alison J. Hanson, Hassina Benchabane, Kenyi Saito-Diaz, Carly R. Cabel, Lily Goldsmith, Muhammad Taha, Aksheta Kanuganti, Victoria H. Ng, George Xu, Fei Ye, Julia Picker, Fillip Port, Michael Boutros, Vivian L. Weiss, David J. Robbins, Curtis A. Thorne, Yashi Ahmed, Ethan Lee
Summary: The Wnt-beta-catenin signal transduction pathway is crucial for embryonic development and adult tissue homeostasis. The deubiquitylase USP47 has been identified as a positive regulator of Wnt signaling by counteracting the E3 ligase activity of XIAP on the transcriptional corepressor Groucho/TLE. This mechanism helps to ensure that the expression of Wnt target genes continues only as long as the upstream signal is present.
Article
Biochemistry & Molecular Biology
Florian Heigwer, Christian Scheeder, Josephine Bageritz, Schayan Yousefian, Benedikt Rauscher, Christina Laufer, Sergi Beneyto-Calabuig, Maja Christina Funk, Vera Peters, Maria Boulougouri, Jana Bilanovic, Thilo Miersch, Barbara Schmitt, Claudia Blass, Fillip Port, Michael Boutros
Summary: This article reports a study that utilizes synthetic genetic interaction and cell morphology data to investigate gene function. They used machine learning to assign functions to genes in 47 modules and identified an interaction between Cdk2 and the Cop9 signalosome complex. These data provide a genome-scale resource for uncovering the mechanisms underlying genetic interactions and their plasticity at the single-cell level.