Article
Multidisciplinary Sciences
Hui Sun, Hui Li, Jie Yan, Xiangdong Wang, Mengyuan Xu, Mingxia Wang, Baozhen Fan, Jieying Liu, Ninghua Lin, Xin Wang, Li Li, Shengtian Zhao, Yongfeng Gong
Summary: Although mature podocytes lack tight junctions, the tight junction integral membrane protein claudin-5 (CLDN5) is predominantly expressed on the plasma membranes of podocytes under normal conditions. The deletion of CLDN5 exacerbates podocyte injury and proteinuria in a diabetic nephropathy mouse model by reducing ZO1 expression, inducing nuclear translocation of ZONAB, and downregulating the expression of WNT inhibitory factor-1 (WIF1).
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Harsha Renikunta, Katina Lazarow, Yiqi Gong, Praphulla Chandra Shukla, Vanasa Nageswaran, Hector Giral, Adelheid Kratzer, Lennart Opitz, Felix B. Engel, Arash Haghikia, Sarah Costantino, Francesco Paneni, Jens Peter von Kries, Katrin Streckfuss-Bomeke, Ulf Landmesser, Philipp Jakob
Summary: Ischemic cardiomyopathy, driven by loss of cardiomyocytes and inadequate proliferative response, is a major global health problem. Functional high-throughput screening revealed that overexpression of certain miRNAs, especially miR-515-3p and miR-519e-3p from the C19MC-cluster, enhanced proliferative activity in hiPSC-CM and altered signaling pathways relevant for cardiomyocyte proliferation.
Article
Multidisciplinary Sciences
Ida Lauritsen, Pernille Ott Frendorf, Silvia Capucci, Sophia A. H. Heyde, Sarah D. Blomquist, Sofie Wendel, Emil C. Fischer, Agnieszka Sekowska, Antoine Danchin, Morten H. H. Norholm
Summary: Microbial evolution often involves transient and complex changes, including sequential adaptive mutations in hotspot genes. This study shows that alterations in pyrimidine nucleoside levels and mutations in metabolic or regulatory genes can drive the evolution of non-growing E. coli cells. The findings highlight the regulatory role of pyrimidine nucleosides in carbon catabolism and the interaction between transcription factors in sensing carbon availability and metabolic flux.
NATURE COMMUNICATIONS
(2021)
Article
Biology
Kornelia Szebenyi, Inigo Barrio-Hernandez, George M. Gibbons, Luca Biasetti, Claire Troakes, Pedro Beltrao, Andras Lakatos
Summary: Interrogation of amyotrophic lateral sclerosis (ALS)-linked GWAS gene networks, astrocyte-based multi-omics datasets and cellular models identifies kinesin motor protein KIF5A as a modifier of astrocyte process integrity and potential target in ALS.
COMMUNICATIONS BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Nathan J. VanDusen, Julianna Y. Lee, Weiliang Gu, Catalina E. Butler, Isha Sethi, Yanjiang Zheng, Justin S. King, Pingzhu Zhou, Shengbao Suo, Yuxuan Guo, Qing Ma, Guo-Cheng Yuan, William William Pu
Summary: The study utilized in vivo somatic Cas9 mutagenesis in mice to conduct a forward genetic screen for regulators of cardiomyocyte maturation, identifying transcriptional regulators such as RNF20 and RNF40. Mechanistic studies showed that these regulators control dynamic gene expression changes essential for cardiomyocyte maturation.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Christer Sylven, Eva Wärdell, Agneta Mänsson-Broberg, Eugenio Cingolani, Konstantinos Ampatzis, Ludvig Larsson, Asa Björklund, Stefania Giacomello
Summary: Human prenatal cardiomyocytes were characterized using single-cell RNA sequencing, spatial transcriptomics, and ligand-receptor interaction information. Eight types of developing cardiomyocytes were identified, more than double the ones in the Human Developmental Cell Atlas. These cells exhibit high variability in cell cycle activity, mitochondrial content, and connexin gene expression, and are differentially distributed in the ventricles and atria. The ligand-receptor crosstalk of cardiomyocytes is mainly with non-cardiomyocyte cell types and involves cardiogenesis-related pathways. Understanding the developmental dynamics of early prenatal human cardiomyocytes may lead to new therapies.
Article
Biochemistry & Molecular Biology
Line Lykke Andersen, Yiqi Huang, Christian Urban, Lila Oubraham, Elena Winheim, Che Stafford, Dennis Nagl, Fionan O'Duill, Thomas Ebert, Thomas Engleitner, Soren Riis Paludan, Anne Krug, Roland Rad, Veit Hornung, Andreas Pichlmair
Summary: The immune system plays a crucial role in maintaining tissue homeostasis and defending against invading pathogens, and extracellular nucleotides are known to contribute to immune signaling specificity. This study focused on the responses of human macrophages to extracellular nucleotides, specifically looking at the P2Y family of nucleotide-sensing GPRC receptors. The findings reveal the important functions of P2Y receptors in regulating both inflammatory and antiviral responses in macrophages.
Article
Genetics & Heredity
Shilong You, Jiaqi Xu, Boquan Wu, Shaojun Wu, Ying Zhang, Yingxian Sun, Naijin Zhang
Summary: This study identified POLR2I as a key gene related to the pathogenesis of hypertensive nephropathy, providing new insights into the molecular mechanisms underlying this disease.
FRONTIERS IN GENETICS
(2021)
Article
Endocrinology & Metabolism
Lei Dai, Yang Xie, Wenjun Zhang, Xiaodan Zhong, Mengwen Wang, Hongcheng Jiang, Zhen He, Xiaolei Liu, Hesong Zeng, Hongjie Wang
Summary: The study identified ANGPTL4 as a key gene associated with diabetic cardiomyopathy, with functional roles in promoting cardiac apoptosis through the FAK/SIRT3/ROS pathway.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Cell Biology
Suraj Kannan, Matthew Miyamoto, Renjun Zhu, Michaela Lynott, Jason Guo, Elaine Zhelan Chen, Alexandre R. Colas, Brian Leei Lin, Chulan Kwon
Summary: A limitation in the application of pluripotent stem cell-derived cardiomyocytes (PSC-CMs) is their failure to achieve full functional maturity. In this study, the authors generated reference maps of mouse in vivo cardiomyocyte maturation and PSC-CM-directed differentiation through single-cell RNA sequencing. They identified an endogenous perinatal maturation program that is poorly recapitulated in vitro and uncovered a network of nine transcription factors consistently dysregulated in PSC-CMs across species. These findings have implications for improving the clinical viability of PSC-CMs.
Article
Biochemistry & Molecular Biology
Tomoyuki Furuya, Masato Saito, Haruka Uchimura, Akiko Satake, Shohei Nosaki, Takuya Miyakawa, Shunji Shimadzu, Wataru Yamori, Masaru Tanokura, Hiroo Fukuda, Yuki Kondo
Summary: Through co-expression network analysis, a new cambium-related regulatory module was identified, including the transcription factor BEH3, which plays a crucial role in the maintenance and stability of vascular stem cells. Further genetic analysis revealed that BEH3 and BES1 perform opposite functions in the regulation of vascular stem cells and the differentiation of vascular cells.
Article
Cell Biology
Julia Steger, Alison G. Cole, Andreas Denner, Tatiana Lebedeva, Grigory Genikhovich, Alexander Ries, Robert Reischl, Elisabeth Taudes, Mark Lassnig, Ulrich Technau
Summary: Using single-cell RNA sequencing in the cnidarian Nematostella vectensis, researchers have discovered that neurons, stinging cells, and gland cells originate from a common multipotent progenitor population. They also identified the conserved transcription factor gene SoxC as a key regulator of all neuroglandular lineages. Unlike vertebrates, the differentiation of neuroglandular cells in the sea anemone is maintained throughout all life stages and follows the same molecular trajectories.
Article
Multidisciplinary Sciences
Jun Jie Tan, Jacques P. Guyette, Kenji Miki, Ling Xiao, Gurbani Kaur, Tong Wu, Liye Zhu, Katrina J. Hansen, King-Hwa Ling, David J. Milan, Harald C. Ott
Summary: The study demonstrates the generation of premature PECs using BVR stimulation, co-culturing PECs with cardiomyocytes leads to cardiomyocyte aggregation, proliferation and the formation of more mature structures with improved beating/contractility.
NATURE COMMUNICATIONS
(2021)
Article
Genetics & Heredity
Changuk Chung, Xiaoxu Yang, Taejeong Bae, Keng Ioi Vong, Swapnil H. Mittal, Catharina Donkels, H. Westley Phillips, Zhen Li, Ashley P. L. Marsh, Martin Breuss, Laurel Ball, Camila Araujo Bernardino Garcia, Renee George, Jing Gu, Mingchu Xu, Chelsea Barrows, Kiely James, Valentina Stanley, Anna Nidhiry, Sami Khoury, Gabrielle Howe, Emily Riley, Xin Xu, Brett Copeland, Yifan G. Wang, Se Hoon L. Kim, Hoon-Chul W. Kang, Andreas Schulze-Bonhage, Carola Haas, Horst Urbach, Marco Prinz, David A. Limbrick, Christina Gurnett, Matthew C. Smyth, Shifteh M. Sattar, Mark B. Nespeca, David V. Gonda, Katsumi Y. Imai, Yukitoshi E. Takahashi, Hsin-Hung B. Chen, Jin-Wu Tsai, Valerio Conti, Renzo Guerrini, Orrin Devinsky, Wilson Silva, Helio M. Machado, Gary Mathern, Alexej Abyzov, Sara Baldassari, Stephanie Baulac, Joseph G. Gleeson
Summary: Malformations of cortical development (MCD) are neurological disorders caused by somatic mosaic mutations during embryogenesis, leading to intractable epilepsy. This study identified 69 mutated genes from 283 brain resections and investigated their functional roles using various techniques. Genotype-phenotype correlation analysis revealed specific gene sets associated with different pathophysiological and clinical phenotypes of MCD. The spatiotemporal expression patterns of mutated genes in control and patient brains suggest their critical roles in excitatory neurogenesis and neuronal hyperexcitability.
Article
Biochemistry & Molecular Biology
Lu Liu, Yuxi Lei, Wensheng Chen, Qian Zhou, Zongyao Zheng, Guandi Zeng, Wanting Liu, Pengju Feng, Zhiyi Zhang, Lei Yu, Liang Chen
Summary: In this study, we identified ZNF24 as a potent tumor suppressor gene in lung cancer. We found that ZNF24 inhibits the activity of NF-kappa B pathway, which is clinically relevant. Furthermore, combinational inhibition of KRAS, NF-kappa B, and PD-1 effectively reduced lung tumor size in mice.
CELL AND BIOSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Gunnar Houge, Andreas Laner, Sebahattin Cirak, Nicole de Leeuw, Hans Scheffer, Johan T. den Dunnen
Summary: The article introduces a scoring-based variant classification model that can be used as an add-on or alternative to the ACMG classification. The system divides variant classification into functional (A) and clinical (B) grades, which are combined to generate a joint class ranging from A to F. This system gives clinicians a better guide to the significance of genetic variants.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Genetics & Heredity
Steven Laurie, Davide Piscia, Leslie Matalonga, Alberto Corvo, Marcos Fernandez-Callejo, Carles Garcia-Linares, Carles Hernandez-Ferrer, Cristina Luengo, Ines Martinez, Anastasios Papakonstantinou, Daniel Pico-Amador, Joan Protasio, Rachel Thompson, Raul Tonda, Monica Bayes, Gemma Bullich, Jordi Camps-Puchadas, Ida Paramonov, Jean-Remi Trotta, Angel Alonso, Marcella Attimonelli, Christophe Beroud, Virginie Bros-Facer, Orion J. Buske, Andres Canada-Pallares, Jose M. Fernandez, Mats G. Hansson, Rita Horvath, Julius O. B. Jacobsen, Rajaram Kaliyaperumal, Severine Lair-Preterre, Luana Licata, Pedro Lopes, Estrella Lopez-Martin, Deborah Mascalzoni, Lucia Monaco, Luis A. Perez-Jurado, Manuel Posada de la Paz, Jordi Rambla, Ana Rath, Olaf Riess, Peter N. Robinson, David Salgado, Damian Smedley, Dylan Spalding, Peter A. C. 't Hoen, Ana Topf, Irina Zaharieva, Holm Graessner, Ivo G. Gut, Hanns Lochmuller, Sergi Beltran
Summary: Rare disease patients are now more likely to receive rapid molecular diagnosis, but some cases still remain undiagnosed. The RD-Connect GPAP provides a standardized platform for data collection, sharing, and analysis to aid in diagnosing cases and discovering new disease causing genes.
Article
Genetics & Heredity
Benjamin Billiet, Patrizia Amati-Bonneau, Valerie Desquiret-Dumas, Khadidja Guehlouz, Dan Milea, Philippe Gohier, Guy Lenaers, Delphine Mirebeau-Prunier, Johan T. den Dunnen, Pascal Reynier, Marc Ferre
Summary: A public database for NR2F1 gene was established to refine the clinical description of BBSOAS, suggesting additional signs and features for neurological and motor functions.
Article
Biochemistry & Molecular Biology
Ana Goncalves, Ana Fortuna, Yavuz Ariyurek, Marcia E. Oliveira, Goreti Nadais, Jorge Pinheiro, Johan T. den Dunnen, Mario Sousa, Jorge Oliveira, Rosario Santos
Summary: In this study, a patient with Becker Muscular Dystrophy was identified to have a DMD gene defect that could not be detected by routine molecular techniques. The application of low-coverage linked-read whole-genome sequencing revealed a possible genomic rearrangement and confirmed the presence of a genomic inversion. This study expands the mutational spectrum of dystrophinopathies and highlights the importance of transcript analysis in diagnosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Vanessa Luiza Romanelli Tavares, Sofia Ligia Guimaraes-Ramos, Yan Zhou, Cibele Masotti, Suzana Ezquina, Danielle de Paula Moreira, Henk Buermans, Renato S. Freitas, Johan T. Den Dunnen, Stephen R. F. Twigg, Maria Rita Passos-Bueno
Summary: The study identified a fourth locus causative of ARCND in a family, represented by a tandem duplication of 430 kb in a candidate region on chromosome 7. The findings support the hypothesis that deregulation of TWIST1 expression during craniofacial development can contribute to the phenotype.
JOURNAL OF MEDICAL GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Sylvia Nieuwenhuis, Joanna Widomska, Paul Blom, Peter-Bram A. C. 't Hoen, Baziel G. M. van Engelen, Jeffrey C. Glennon
Summary: The blood transcriptome was examined in relation to disease severity in type I myotonic dystrophy (DM1) patients. It was found that changes in transcriptome, particularly in innate and adaptive immunity associated with muscle-wasting, were linked to symptom severity in DM1. Further studies should investigate the role of immunity in DM1.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Dario F. Marzella, Farzaneh M. Parizi, Derek Van Tilborg, Nicolas Renaud, Daan Sybrandi, Rafaella Buzatu, Daniel T. Rademaker, Peter A. C. 't Hoen, Li C. Xue
Summary: A deeper understanding of T-cell-mediated adaptive immune responses is crucial for cancer immunotherapy and antiviral vaccine design. Researchers have developed PANDORA, a generic modelling pipeline for pMHC-I and pMHC-II, which shows excellent performance in pMHC-I modelling.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
K. Joeri van der Velde, Gurnoor Singh, Rajaram Kaliyaperumal, Xiaofeng Liao, Sander de Ridder, Susanne Rebers, Hindrik H. D. Kerstens, Fernanda de Andrade, Jeroen van Reeuwijk, Fini E. De Gruyter, Saskia Hiltemann, Maarten Ligtvoet, Marjan M. Weiss, Hanneke W. M. van Deutekom, Anne M. L. Jansen, Andrew P. Stubbs, Lisenka E. L. M. Vissers, Jeroen F. J. Laros, Esther van Enckevort, Daphne Stemkens, Peter A. C. t Hoen, Jeroen A. M. Belien, Marielle E. van Gijn, Morris A. Swertz
Summary: FAIR Genomes aims to facilitate the reuse of genomic data by developing metadata standards and providing templates for data entry and programmatic interfaces. It addresses the challenge of storing and sharing genomic data by offering a semantic schema for data descriptions. With FAIR Genomes, rare disease diagnosis and personalized medicine research can be enhanced.
Article
Mathematical & Computational Biology
Renee X. de Menezes, Armin Rauschenberger, Bios Consortium, Peter A. C. 't Hoen, Marianne A. Jonker
Summary: This article introduces a score-based test method that takes into account the effects of all exons and all SNPs on exon inclusion simultaneously. The test method is computationally efficient and can be used when the number of SNPs is larger than the number of samples. It is also more robust to exon-SNP pair-specific effects.
BIOMETRICAL JOURNAL
(2023)
Editorial Material
Genetics & Heredity
Andreas Laner, Ales Maver, Johan T. den Dunnen
Summary: The journal Human Mutation focuses on variants in the human genome and aims to understand the consequences of carrying a variant for individual health. This article collection provides insights into the advancements and limitations in variant effect prediction, aiming to improve our understanding of genotype-phenotype relationships.
Article
Biology
Tooba Abbassi-Daloii, Salma el Abdellaoui, Lenard M. Voortman, Thom T. J. Veeger, Davy Cats, Hailiang Mei, Duncan E. Meuffels, Ewoud van Arkel, Peter Bram 't Hoen, Hermien Kan, Vered Raz
Summary: We constructed a large atlas of RNA-seq profiles from leg muscles, identifying differential expression patterns and cellular composition across different tissues. The muscle samples were clustered into three groups based on anatomical location, which were associated with oxidative metabolism and fast- or slow-twitch myofibers. Expression profiles of Homeobox transcription factors differed between the three groups. Our study provides a novel resource to study muscle-specific molecular features and their potential links to physiological processes.
Meeting Abstract
Biochemistry & Molecular Biology
Tabea V. Riepe, Mubeen Khan, Susanne Roosing, Frans P. M. Cremers, Peter A. C. t Hoen
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Stefan Aretz, Isabel Spier, Xiaoyu Sherry Yin, John-Paul Plazzer, Elke Holinski-Feder, Johan T. den Dunnen, Deborah Ritter, Sharon Plon, Marc Greenblatt, Ian Frayling, Finlay A. Macrae
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Pablo Beckers, Jean-Hubert Caberg, Vinciane Dideberg, Johan T. den Dunnen, Tamara Dangouloff, Vincent Bours, Laurent Servais, Francois Boemer
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Genetics & Heredity
Max J. F. Degener, Remco T. P. van Cruchten, Brittney A. Otero, Eric T. Wang, Derick G. Wansink, Peter A. C. 't Hoen
Summary: In patients with myotonic dystrophy type 1 (DM1), dysregulation of RNA-binding proteins leads to alternative splicing patterns similar to fetal ones, and this dysregulation is associated with changes in mRNA expression of splice regulators MBNL1, MBNL2 and CELF1.
NAR GENOMICS AND BIOINFORMATICS
(2022)
