Article
Multidisciplinary Sciences
Laura M. Pikkupeura, Raul B. Bressan, Jordi Guiu, Yun Chen, Martti Maimets, Daniela Mayer, Pawel J. Schweiger, Stine L. Hansen, Grzegorz J. Maciag, Hjalte L. Larsen, Kadi Lohmussaar, Marianne Terndrup Pedersen, Joji M. Yap Teves, Jette Bornholdt, Vladimir Benes, Albin Sandelin, Kim B. Jensen
Summary: During intestinal organogenesis, the maturation of intestinal stem cells is not fully understood. In this study, we used intestinal organoid cultures to analyze the transcriptional, chromatin accessibility, DNA methylation, and three-dimensional chromatin conformation landscapes in fetal and adult epithelial cells. We found differences in gene expression, enhancer activity, 3D organization, DNA accessibility, and methylation between the two states. We identified sustained Yes-Associated Protein (YAP) activity as a major regulator of the immature fetal state, likely coordinated by changes in extracellular matrix composition.
Article
Multidisciplinary Sciences
Zhifen Zhou, Yujing Li, Huimin Xu, Xiaowei Xie, Zibin He, Song Lin, Ruofei Li, Shouheng Jin, Jun Cui, Hai Hu, Feng Liu, Su Wu, Wenbin Ma, Zhou Songyang
Summary: This study identified multiple positive regulators, including the E3 ligase DTX2, through an inducible CRISPR/Cas9 KO screen. Depletion of DTX2 in telomerase-positive cancer cells resulted in downregulation of hTERT transcription and telomerase activity, leading to progressive telomere shortening, growth arrest, and increased apoptosis. BioID analysis revealed that DTX2 interacts with multiple transcription factors, with NFIC functioning cooperatively with DTX2 to promote hTERT transcription. Further investigation demonstrated that DTX2 mediates K63-linked ubiquitination of NFIC, which enhances NFIC binding to the hTERT promoter and increases hTERT expression.
Article
Biology
Ibrahim Ahmed, Shen-Hsi Yang, Samuel Ogden, Wei Zhang, Yaoyong Li, Andrew D. Sharrocks, William C. Hahn
Summary: This article utilizes RNA-seq data and open chromatin maps to identify potential enhancer RNAs and associated enhancer regions in oesophageal adenocarcinoma. It discovers OAC-specific enhancers and uncovers new cellular pathways operative in OAC. The study also demonstrates the clinical utility of the dataset for disease stage identification and patient prognosis.
Article
Neurosciences
Florian Noack, Silvia Vangelisti, Gerald Raffl, Madalena Carido, Jeisimhan Diwakar, Faye Chong, Boyan Bonev
Summary: By studying multiple epigenetic layers and enhancer activity in mouse cortical development, the authors identify Neurog2 as a key transcription factor that drives the remodeling of the regulatory landscape. By profiling gene expression, chromatin accessibility, enhancer activity, DNA methylation, and three-dimensional genome architecture, they identify thousands of new enhancers, their target genes, and the temporal relationships between enhancer activation, epigenome remodeling, and gene expression. They also discover specific neuronal transcription factors that play a role in coordinating changes across multiple epigenetic modalities. Additionally, they demonstrate a new role for Neurog2 in directly mediating enhancer activity, DNA demethylation, increasing chromatin accessibility, and facilitating chromatin looping in vivo. This study provides a comprehensive understanding of the gene regulatory logic in cortical lineage specification.
NATURE NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Lounis Yakhou, Anaelle Azogui, Nikhil Gupta, Julien Richard Albert, Fumihito Miura, Laure Ferry, Kosuke Yamaguchi, Sarah Battault, Pierre Therizols, Frederic Bonhomme, Elouan Bethuel, Arpita Sarkar, Maxim V. C. Greenberg, Paola B. Arimondo, Gael Cristofari, Olivier Kirsh, Takashi Ito, Pierre-Antoine Defossez
Summary: Epigenetic mechanisms play crucial roles in establishing and maintaining cellular identities in mammals. They regulate the expression of genes, transposable elements, and chromatin structures, and are essential for mammalian development. Bivalent promoters are particularly important during differentiation and development. BEND3 has been identified as a regulator of bivalent promoters, and its absence leads to genome-wide DNA methylation gains and reduced DNA hydroxymethylation, suggesting its direct and indirect roles in chromatin regulation.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Cell Biology
Jieqiong Qu, Valerie Betting, Ruben van Iterson, Florence M. Kwaschik, Ronald P. van Rij
Summary: The piRNA pathway in mosquitoes is characterized by an expanded PIWI gene family and antiviral defense functions. Core piRNA clusters, which are enriched for non-retroviral endogenous viral elements (nrEVEs), show ubiquitous expression in both somatic and germline tissues and depend on key biogenesis factors. Transcriptional readthrough is identified as a conserved mechanism for cluster-derived piRNA biogenesis in vector mosquitoes. These findings provide a foundation for further investigation of gene regulation, genome evolution, and piRNA function in important vector species.
Article
Oncology
Qiaoming Zhi, Daiwei Wan, Rui Ren, Zhihua Xu, Xiaobo Guo, Ye Han, Fei Liu, Ye Xu, Lei Qin, Yilin Wang
Summary: The study revealed that circ102049 plays a significant role in colorectal cancer liver metastasis by promoting CRC progression via the miR-761/miR-192-3p-FRAS1-dependent mechanism. Additionally, circ102049 may indirectly affect the levels of mature miR-761 and miR-192-3p in the cytoplasm through the distribution of DGCR8 protein.
MOLECULAR ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
John Verigos, Dimitris Kordias, Styliani Papadaki, Angeliki Magklara
Summary: Cancer stem cells play a significant role in chemoresistance, tumor recurrence, and metastasis in breast cancer, making them a promising target for new therapies. Through RNA-sequencing, researchers identified differential gene expression patterns between breast CSCs and non-CSCs, with the TRPM4 gene being found to be overexpressed in tumorspheres and affecting stemness properties. Inhibiting TRPM4 showed potential anti-tumor effects by targeting the bCSC subpopulation, suggesting a novel therapeutic approach for improving breast cancer treatments.
Article
Immunology
Noam Kadouri, Tal Givony, Shir Nevo, Joschka Hey, Shifra Ben Dor, Golda Damari, Bareket Dassa, Jan Dobes, Dieter Weichenhan, Marion Bahr, Michelle Paulsen, Rebecca Haffner-Krausz, Marcus A. Mall, Christoph Plass, Yael Goldfarb, Jakub Abramson
Summary: This study reveals the importance of FOXN1 in the development of thymic epithelial cells and hair follicle cells, and identifies key regulatory regions and transcription factors involved in its expression.
SCIENCE IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Mingyuan Du, Cristina Espinosa-Diez, Mingjun Liu, Ibrahim Adeola Ahmed, Sidney Mahan, Jianxin Wei, Adam L. Handen, Stephen Y. Chan, Delphine Gomez
Summary: miRNAs play versatile roles in regulating smooth muscle cell fate and behavior during vascular development and disease. The miR-200 cluster is found to be downregulated during SMC dedifferentiation and acts as a mechanism to maintain SMC quiescence and inhibit proliferation, migration, and neointima formation by targeting Quaking.
Article
Biochemistry & Molecular Biology
Christina B. Bielmeier, Saskia Roth, Sabrina Schmitt, Stefaniya K. Boneva, Anja Schlecht, Mario Vallon, Ernst R. Tamm, Sueleyman Erguen, Andreas Neueder, Barbara M. Braunger
Summary: In this study, the transcriptional profile of mice carrying a model for autosomal dominant RP was characterized using RNASeq and WGCNA analysis. Dysregulated genes and gene modules associated with TGF-beta regulated pathways, immune response, and cellular homeostasis were identified. The study suggested that VPP-induced retinal degeneration may primarily involve neuroinflammation and activation of neuroprotective signaling pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Kathrin Gianmoena, Nina Gasparoni, Adelina Jashari, Philipp Gabrys, Katharina Grgas, Ahmed Ghallab, Karl Nordstroem, Gilles Gasparoni, Joerg Reinders, Karolina Edlund, Patricio Godoy, Alexander Schriewer, Heiko Hayen, Christian A. Hudert, Georg Damm, Daniel Seehofer, Thomas S. Weiss, Peter Boor, Hans-Joachim Anders, Manga Motrapu, Peter Jansen, Tobias S. Schiergens, Maren Falk-Paulsen, Philip Rosenstiel, Clivia Lisowski, Eduardo Salido, Rosemarie Marchan, Joern Walter, Jan G. Hengstler, Cristina Cadenas
Summary: Epigenetic modifications in NAFLD, particularly in glyoxylate metabolism, contribute to kidney damage via oxalate release. The downregulation and hypermethylation of AGXT in steatotic hepatocytes lead to elevated oxalate levels, explaining the increased risk of kidney stones and chronic kidney disease in NAFLD patients.
Article
Oncology
Anna Strzeszewska-Potyrala, Karolina Staniak, Joanna Czarnecka-Herok, Mahmoud-Reza Rafiee, Marcin Herok, Grazyna Mosieniak, Jeroen Krijgsveld, Ewa Sikora
Summary: The study identified ZNF84 as a critical regulator of senescence in p53-mutated tumors, showing that its knock-down inhibited p21 expression and increased proliferation, while also reducing genotoxic effects of doxorubicin. Additionally, ZNF84 deficiency was associated with changes in transcriptomic profiles and lower survival rates in colon cancer patients, suggesting its potential as a target for novel therapies in p53-null cancers.
Article
Genetics & Heredity
Antje K. Rottner, Yingying Ye, Elena Navarro-Guerrero, Varsha Rajesh, Alina Pollner, Romina J. Bevacqua, Jing Yang, Aliya F. Spigelman, Roberta Baronio, Austin Bautista, Soren K. Thomsen, James Lyon, Sameena Nawaz, Nancy Smith, Agata Wesolowska-Andersen, Jocelyn E. Manning Fox, Han Sun, Seung K. Kim, Daniel Ebner, Patrick E. MacDonald, Anna L. Gloyn
Summary: Through a genome-wide CRISPR loss-of-function screen, we identified 580 genes associated with type 2 diabetes (T2D) and found 20 candidate transcripts, including the autophagy receptor CALCOCO2, which were supported by genetic and genomic data. Loss of CALCOCO2 led to distorted mitochondria, accumulation of immature proinsulin-containing granules, and autophagosome accumulation upon late-stage autophagy inhibition. Carriers of T2D-associated CALCOCO2 variants also showed altered insulin secretion.
Article
Multidisciplinary Sciences
Iman Lohraseb, Peter McCarthy, Genevieve Secker, Ceilidh Marchant, Jianmin Wu, Naveid Ali, Sharad Kumar, Roger J. Daly, Natasha L. Harvey, Hiroshi Kawabe, Oded Kleifeld, Sophie Wiszniak, Quenten Schwarz
Summary: This study uncovers the important role of NEDD4-mediated ubiquitination in neural crest cell development, regulating the ubiquitination and turnover of Profilin 1 to modulate actin polymerization.
NATURE COMMUNICATIONS
(2022)
Review
Medicine, Research & Experimental
Nastazja Dagny Pilonis, Marc Tischkowitz, Rebecca C. Fitzgerald, Massimiliano di Pietro
Summary: Hereditary diffuse gastric cancer (HDGC) is a rare cancer syndrome associated with significant risks of gastric and lobular breast cancer, often presenting late in clinical settings. While most cases can be traced back to germline variants in the CDH1 gene, some families with clustering of DGC do not have a clear genetic cause. This review focuses on discussing key elements for assessing inherited DGC susceptibility, providing practical recommendations for surveillance and treatment of at-risk individuals and early-stage patients.
ANNUAL REVIEW OF MEDICINE, VOL 72, 2021
(2021)
Article
Gastroenterology & Hepatology
Swathi Eluri, Anna Paterson, Brianna N. Lauren, Maria O'Donovan, Pradeep Bhandari, Massimiliano di Pietro, Minyi Lee, Rehan Haidry, Laurence Lovat, Krish Ragunath, Chin Hur, Rebecca C. Fitzgerald, Nicholas J. Shaheen
Summary: This study assessed the application value of Cytosponge in BE patients after RFA. The results showed that Cytosponge testing is a cost-effective surveillance method and is strongly associated with residual BE after ablation.
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Gastroenterology & Hepatology
Elizabeth Ratcliffe, James Britton, Shaheen Hamdy, John McLaughlin, Yeng Ang
Summary: This review explores the emerging role of dedicated services for patients with Barrett's oesophagus (BO). The research indicates that dedicated services can improve guideline adherence and increase dysplasia detection rates. Additionally, patients report high levels of cancer worry and poor disease-specific knowledge.
BMJ OPEN GASTROENTEROLOGY
(2022)
Review
Biochemistry & Molecular Biology
Rebecca C. Fitzgerald, Antonis C. Antoniou, Ljiljana Fruk, Nitzan Rosenfeld
Summary: Proactively detecting cancer at an early stage is crucial, but distinguishing inconsequential changes from life-threatening lesions can be challenging. Advancements in technology will aid real-time detection of personalized cancer signals. Risk-based detection and prevention should be cost effective and widely accessible.
Review
Multidisciplinary Sciences
David Crosby, Sangeeta Bhatia, Kevin M. Brindle, Lisa M. Coussens, Caroline Dive, Mark Emberton, Sadik Esener, Rebecca C. Fitzgerald, Sanjiv S. Gambhir, Peter Kuhn, Timothy R. Rebbeck, Shankar Balasubramanian
Summary: Early detection of cancer is crucial for improving survival rates, but unfortunately, a significant number of cases are diagnosed at an advanced stage. Overcoming various challenges is essential to achieve early detection for all cancers, including understanding high-risk individuals, elucidating the biology and trajectory of precancer and early cancer, and developing sensitive and specific detection technologies.
Article
Biology
Alvin Wei Tian Ng, Gianmarco Contino, Sarah Killcoyne, Ginny Devonshire, Ray Hsu, Sujath Abbas, Jing Su, Aisling M. Redmond, Jamie M. J. Weaver, Matthew D. Eldridge, Simon Tavare, Paul A. W. Edwards, Rebecca C. Fitzgerald
Summary: This study categorizes genomic structural variants (SVs) in 383 cases of oesophageal cancer, uncovering mutational patterns and new disease drivers. Identification of SV events in OAC is crucial for targeted therapies.
COMMUNICATIONS BIOLOGY
(2022)
Article
Surgery
Ajith K. Siriwardena
Summary: This study provides a global overview of the management of patients with acute cholecystitis during the early phase of the COVID-19 pandemic. The pandemic led to a decrease in surgical workforce and operating facilities, worse severity of disease, and increased use of conservative management. While the number of patients undergoing cholecystectomy decreased, there was no increase in post-operative mortality.
Article
Oncology
Xiaoyu Wang, Puya Gharahkhani, David M. Levine, Rebecca C. Fitzgerald, Ines Gockel, Douglas A. Corley, Harvey A. Risch, Leslie Bernstein, Wong-Ho Chow, Lynn Onstad, Nicholas J. Shaheen, Jesper Lagergren, Laura J. Hardie, Anna H. Wu, Paul D. P. Pharoah, Geoffrey Liu, Lesley A. Anderson, Prasad G. Iyer, Marilie D. Gammon, Carlos Caldas, Weimin Ye, Hugh Barr, Paul Moayyedi, Rebecca Harrison, R. G. Peter Watson, Stephen Attwood, Laura Chegwidden, Sharon B. Love, David MacDonald, John DeCaestecker, Hans Prenen, Katja Ott, Susanne Moebus, Marino Venerito, Hauke Lang, Rupert Mayershofer, Michael Knapp, Lothar Veits, Christian Gerges, Josef Weismueller, Matthias Reeh, Markus M. Noethen, Jakob R. Izbicki, Hendrik Manner, Horst Neuhaus, Thomas Roesch, Anne C. Boehmer, Arnulf H. Hoelscher, Mario Anders, Oliver Pech, Brigitte Schumacher, Claudia Schmidt, Thomas Schmidt, Tania Noder, Dietmar Lorenz, Michael Vieth, Andrea May, Timo Hess, Nicole Kreuser, Jessica Becker, Christian Ell, Ian Tomlinson, Claire Palles, Janusz A. Jankowski, David C. Whiteman, Stuart MacGregor, Johannes Schumacher, Thomas L. Vaughan, Matthew F. Buas, James Y. Dai
Summary: This study identified novel genetic susceptibility loci for esophageal adenocarcinoma and Barrett esophagus using an eQTL set-based genetic association approach, expanding the pool of genetic susceptibility loci.
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2022)
Review
Geriatrics & Gerontology
Patrick Casey, Mohamed Alasmar, John McLaughlin, Yeng Ang, Jamie McPhee, Priam Heire, Javed Sultan
Summary: Ultrasound is a promising tool for measuring skeletal muscle mass and quality, and can predict functional capacity, clinical outcomes, and survival. However, further standardization is needed before ultrasound can be widely used in nutritionally vulnerable patients.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2022)
Article
Pathology
Maja Kopczynska, Elizabeth Ratcliffe, Harika Yalamanchili, Anna Thompson, Adib Nimri, James Britton, Yeng Ang
Summary: IDD in Barrett's esophagus carries a significant risk of progression to dysplasia or neoplasia, highlighting the importance of accurate histological reporting for diagnosis and management.
JOURNAL OF CLINICAL PATHOLOGY
(2022)
Article
Multidisciplinary Sciences
Lorea Valcarcel-Jimenez, Connor Rogerson, Cissy Yong, Christina Schmidt, Ming Yang, Monica Cremades-Rodelgo, Victoria Harle, Victoria Offord, Kim Wong, Ariane Mora, Alyson Speed, Veronica Caraffini, Maxine Gia Binh Tran, Eamonn R. Maher, Grant D. Stewart, Sakari Vanharanta, David J. Adams, Christian Frezza
Summary: Depletion of HIRA enhances proliferation and invasion of Fh1-deficient cells by activating MYC and its target genes, leading to increased nucleotide metabolism specifically in Fh1-deficient cells. This finding is instrumental for understanding the mechanisms of tumorigenesis in HLRCC and developing targeted treatments for patients.
Article
Oncology
Colin Y. C. Lee, Adriaan Olivier, Judith Honing, Anne-Marie Lydon, Susan Richardson, Maria O'Donovan, Marc Tischkowitz, Rebecca C. Fitzgerald, Massimiliano di Pietro
Summary: Hereditary diffuse gastric cancer, caused by CDH1 gene mutations, is characterized by early-onset signet ring cell carcinoma. Prophylactic total gastrectomy is the recommended treatment. This study assessed different sampling strategies for detecting signet ring cell carcinoma and identified criteria for characterizing endoscopic lesions in hereditary diffuse gastric cancer.
Article
Oncology
Judith Honing, Rebecca C. Fitzgerald
Summary: Barrett's esophagus is a precancerous condition that can progress to esophageal adenocarcinoma. Surveillance is needed to detect progression, but current methods are limited. This commentary proposes incorporating new risk factors and tools, such as nonendoscopic triage and commercial biomarker panels, into clinical practice for better risk stratification.
CANCER PREVENTION RESEARCH
(2023)
Article
Cell Biology
Connor Rogerson, Marco Sciacovelli, Lucas A. Maddalena, Andromachi Pouikli, Marc Segarra-Mondejar, Lorea Valcarcel-Jimenez, Christina Schmidt, Ming Yang, Elena Ivanova, Joshua Kent, Ariane Mora, Danya Cheeseman, Jason S. Carroll, Gavin Kelsey, Christian Frezza
Summary: Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a cancer syndrome caused by inactivating germ-line mutations in fumarate hydratase (FH) and subsequent accumulation of fumarate. Fumarate accumulation leads to profound epigenetic changes and the activation of an antioxidant response via nuclear translocation of the transcription factor NRF2. The identification of FOXA2 as an antioxidant regulator provides additional insights into the molecular mechanisms behind cell responses to fumarate accumulation and potentially provides further avenues for therapeutic intervention for HLRCC.
Article
Biochemistry & Molecular Biology
Kieran Foley, David Shorthouse, Eric Rahrmann, Lizhe Zhuang, Ginny Devonshire, Rebecca C. OCCAMS Consortium, Rebecca C. Fitzgerald, Benjamin A. Hall
Summary: Metastasis in oesophageal adenocarcinoma (OAC) is a crucial factor affecting survival. Radiological staging is commonly used to assess metastases, but its accuracy is limited. This study analyzed lymph node metastases and identified new roles of genes SMAD4 and KCNQ3 in metastasis. The findings suggest that both genes could serve as novel biomarkers for metastatic risk and offer potential new targets for drug treatment.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
