Article
Genetics & Heredity
Viviana Barra, Roberta Flavia Chiavetta, Simona Titoli, Ivana Maria Provenzano, Pietro Salvatore Carollo, Aldo Di Leonardo
Summary: Curcumin induces senescence in cancer cells and flavonoids can clear these curcumin-induced senescent cancer cells.
Article
Cell Biology
Mutaz A. Abd Al-razaq, Benjamin M. Freyter, Anna Isermann, Gargi Tewary, Adele Mangelinck, Carl Mann, Claudia E. Ruebe
Summary: This study analyzed the epigenetic mechanism of histone variant H2A.J in radiation-induced senescence. The results showed that differential incorporation of H2A.J affects chromatin organization and the epigenetic state of senescence, influencing transcription factor recruitment and inflammatory gene expression, leading to an altered SASP secretome. In lung parenchyma, pneumocytes display dose-dependent H2A.J expression in response to radiation-induced DNA damage, contributing to pro-inflammatory tissue reactions.
Article
Multidisciplinary Sciences
Jorine M. Eeftens, Manya Kapoor, Davide Michieletto, Clifford P. Brangwynne
Summary: Polycomb complex PRC1 forms multicomponent condensates through phase separation, preferentially seeding at H3K27me3 marks and subsequent histone modifications. Inducing Polycomb phase separation can cause chromatin compaction, but the condensates are dispensable for maintaining the compacted state.
NATURE COMMUNICATIONS
(2021)
Review
Genetics & Heredity
Pierre Caron, Enrico Pobega, Sophie E. Polo
Summary: Recent studies have revealed the essential role of heterochromatin marks and associated factors in DNA double-strand break (DSB) repair pathways, influencing repair pathway choice within the nucleus. Heterochromatin features can affect DSB repair pathway choice and support repair processes within the cell nucleus.
FRONTIERS IN GENETICS
(2021)
Review
Biochemical Research Methods
Elias Orouji, Ayush T. Raman
Summary: The human genome is shaped by a variety of histone modifications, which play a crucial role in determining chromatin states and organization. Using statistical models and computational tools, noncoding regions of DNA can be annotated and combinatorial histone marks inferred. These marks enable the discovery of genomic function and activity, and their patterns change in different cell conditions.
BRIEFINGS IN BIOINFORMATICS
(2022)
Review
Oncology
Jason Lin, Shang-Chuen Wu
Summary: This review examines the role of protein serotonylation in transcriptional regulation, its potential impact on the epigenetic landscape, and its implications in lung and other types of cancer. The review discusses the mechanistic details of serotonylation and its connections to the epigenome, as well as the role of transglutaminase 2, in order to guide the development of optimized histone deacetylase inhibitor designs or combination therapies for cancer treatment.
Article
Medicine, Research & Experimental
Xunshan Ren, Huangming Zhuang, Fuze Jiang, Yuelong Zhang, Panghu Zhou
Summary: This study identified AURKB as a key regulator of senescence-associated chromatin in osteoarthritis (OA). Abnormal mechanical strain increased AURKB levels through the Piezo1/Ca2+ signaling axis, leading to heterochromatin instability and senescence in chondrocytes. Inhibition of AURKB by Barasertib reversed senescence and heterochromatin instability and alleviated OA in a rat model.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Cell Biology
Aidan J. Levinsky, Gregor McEdwards, Nasha Sethna, Mark A. Currie
Summary: H3K9 methyltransferases play crucial roles in genome stability, cell type-specific gene expression, and non-histone methylation. They are involved in histone modification and regulate the methylation of various non-histone targets, contributing to genome regulation and cellular functions.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Medicine, Research & Experimental
Tian-Xia Jiang, Shuang Ma, Xia Han, Zi-Yu Luo, Qian-Qian Zhu, Tomoki Chiba, Wei Xie, Kui Lin, Xiao-Bo Qiu
Summary: The research revealed that PA200 plays a crucial role in maintaining the stability of histone marks by promoting the degradation of core histones. Deficiency of PA200 leads to aging-related diseases, such as immune malfunction and shorter lifespan.
Article
Biochemistry & Molecular Biology
Loris Pratx, Philipp Wendering, Christian Kappel, Zoran Nikoloski, Isabel Baeurle
Summary: Heat stress memory in plants is characterized by transcriptional memory and hyper-methylation of histone H3 lysine 4. Reduced histone turnover at these genes is found to contribute to maintaining epigenetic memory. Histone turnover at individual loci was determined by measuring incorporation and retention of an inducible tagged H3.3. Heat stress memory genes exhibit lower histone turnover compared to early heat stress genes. Histone retention/recycling promotes environmentally mediated epigenetic memory.
Review
Biochemistry & Molecular Biology
Anna Kajdy, Jan Modzelewski, Aneta Cymbaluk-Ploska, Ewa Kwiatkowska, Magdalena Bednarek-Jedrzejek, Dariusz Borowski, Katarzyna Stefanska, Michal Rabijewski, Andrzej Torbe, Sebastian Kwiatkowski
Summary: Accelerated placental senescence is crucial in pregnancy pathologies, leading to fetal growth restriction and stillbirth. Aging of the placenta results in decreased cell function and accumulation of senescent cells in mitotic tissues.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Joyce Taylor-Papadimitriou, Joy M. Burchell
Summary: This review focuses on the role of PcG and TrxG complexes in the epigenetic regulation of gene expression and discusses the regulation of suppressive and active marks by methylases and demethylases. Mutations in histone methylases and demethylases in cancer can lead to repression of genes or activation of oncogenes.
Article
Genetics & Heredity
Yukiko Kuroda, Aiko Iwata-Otsubo, Kerith-Rae Dias, Suzanna E. L. Temple, Koji Nagao, Lachlan De Hayr, Ying Zhu, Shin-Ya Isobe, Gohei Nishibuchi, Sarah K. Fiordaliso, Yuki Fujita, Alyssa L. Rippert, Samuel W. Baker, Marco L. Leung, Daniel C. Koboldt, Adele Harman, Beth A. Keena, Izumi Kazama, Gopinath Musuwadi Subramanian, Kandamurugu Manickam, Betsy Schmalz, Maeson Latsko, Elaine H. Zackai, Matt Edwards, Carey-Anne Evans, Matthew C. Dulik, Michael F. Buckley, Toshihide Yamashita, W. Timothy O'Brien, Robert J. Harvey, Chikashi Obuse, Tony Roscioli, Kosuke Izumi
Summary: This study identified heterozygous de novo variants in the CBX1 gene, encoding HP1β, as a cause of a novel syndromic neurodevelopmental disorder. In vitro cellular assays, neurobehavioral and cytological analyses of neuronal cells, and mouse models confirmed the pathogenicity of the identified variants. The disruption of HP1β chromatin binding during neurocognitive development contributes to developmental disabilities.
GENETICS IN MEDICINE
(2023)
Review
Oncology
Colin McCornack, Timothy Woodiwiss, Angela Hardi, Hiroko Yano, Albert H. Kim
Summary: This review discusses the role of histone posttranslational modifications in the pathogenesis and regulation of glioblastoma (GBM) and explores future research directions.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Brendan Moran, Maria Davern, John V. Reynolds, Noel E. Donlon, Joanne Lysaght
Summary: Many cancers can suppress the immune response, but research on histone deacetylase inhibitors (HDACi) has shown potential in reversing these mechanisms and reactivating the immune system for therapeutic benefits. Recent clinical approvals have been given to four HDACi for various malignancies. However, little is known about the impact of HDACi on immune cells and how they interact with other anticancer therapies. This review explores the effects of HDACi on immune cells and provides an overview of clinical trials investigating their combination with chemotherapy, radiotherapy, immunotherapy, and multi-modal regimens.
Review
Biochemistry & Molecular Biology
Eleanor Sheekey, Masashi Narita
Summary: The tumour suppressor p53 plays a central role in cellular senescence by regulating both senescence-associated stable proliferative arrest and the secretion of bioactive factors known as the senescence-associated secretory phenotype (SASP). Senescence is associated with various physiological and pathological conditions, including ageing, cancer, and other age-related disorders. Cell functions are determined by the expression of lineage-specific genes, which are also influenced by p53. Additionally, p53 is tightly regulated at the protein level, and its activity is sustained and fine-tuned during senescence and other prolonged pathological conditions.
Editorial Material
Clinical Neurology
Hsin-Pin Lin, Derek P. Narendra
Summary: This scientific commentary discusses the study by Smajic et al. on single-cell sequencing of the human midbrain, which reveals glial activation and a Parkinson-specific neuronal state.
Article
Clinical Neurology
William Zhu, Xiaoping Huang, Esther Yoon, Sara Bandres-Ciga, Cornelis Blauwendraat, Kimberly J. Billingsley, Joshua H. Cade, Beverly P. Wu, Victoria H. Williams, Alice B. Schindler, Janet Brooks, J. Raphael Gibbs, Dena G. Hernandez, Debra Ehrlich, Andrew B. Singleton, Derek P. Narendra
Summary: Based on a comprehensive analysis of PRKN mutations, this study finds that heterozygous pathogenic PRKN mutations are common in the population but do not increase the risk of Parkinson's disease. This has implications for gene and cell replacement therapies for Parkinson's disease.
Article
Cell Biology
Kelvin Yin, Daniel Patten, Sarah Gough, Susana de Barros Goncalves, Adelyne Chan, Ioana Olan, Liam Cassidy, Marta Poblocka, Haoran Zhu, Aaron Lun, Martijn Schuijs, Andrew Young, Celia Martinez-Jimenez, Timotheus Y. F. Halim, Shishir Shetty, Masashi Narita, Matthew Hoare
Summary: Senescence is a stress-responsive tumor suppressor mechanism associated with the expression of the senescence-associated secretory phenotype (SASP). Through SASP, senescent cells trigger their own immune-mediated elimination, which is prevented by the endothelium. This study demonstrates that SASP induces endothelial cell NF-kappa B activity and that this activity regulates immune cell recruitment and senescence surveillance. Furthermore, oncogenic hepatocyte senescence also influences endothelial NF-kappa B activity in vivo.
GENES & DEVELOPMENT
(2022)
Review
Cell Biology
Ioana Olan, Masashi Narita
Summary: Cellular senescence is a crucial factor in physiological and pathological conditions throughout an organism's lifetime, particularly in aging and age-associated disorders. The impact of senescent cells goes beyond their loss of function and involves substantial alterations in cellular activities, especially the secretion of factors, which affect surrounding tissues and even the entire organism. This non-cell-autonomous functionality is coordinated by tissue-specific genes, determining cell fate.
ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Oncology
Liam D. Cassidy, Masashi Narita
Summary: Autophagy is a crucial process for maintaining cellular homeostasis and preventing aging. It also plays a role in tumor development. Autophagy is involved in maintaining stem cell populations and inhibiting cellular senescence, but the decline in autophagy with age may promote tumor growth.
MOLECULAR ONCOLOGY
(2022)
Article
Oncology
Khoosheh Khayati, Vrushank Bhatt, Taijin Lan, Fawzi Alogaili, Wenping Wang, Enrique Lopez, Zhixian Sherrie Hu, Samantha Gokhale, Liam Cassidy, Masashi Narita, Ping Xie, Eileen White, Jessie Yanxiang Guo
Summary: Autophagy is an important process in maintaining cellular homeostasis and plays a role in the growth and treatment of lung cancer. Systemic autophagy supports tumor cell metabolism and immune evasion in lung cancer, and the inability of tumors to recover from loss of autophagy provides evidence for the effectiveness of autophagy inhibition in cancer therapy.
Article
Multidisciplinary Sciences
Yangteng Ou, Shixiang Cao, Yang Zhang, Hongjia Zhu, Chengzhi Guo, Wei Yan, Fengxue Xin, Weiliang Dong, Yanli Zhang, Masashi Narita, Ziyi Yu, Tuomas P. J. Knowles
Summary: The authors use a core-shell microgel ink to produce functional materials with a range of potential applications, overcoming the challenge of controlling cell microenvironments in extrusion bioprinting.
NATURE COMMUNICATIONS
(2023)
Article
Engineering, Biomedical
Hongjia Zhu, Lianne W. Y. Roode, Aled J. Parry, Nadia A. Erkamp, Marc Rodriguez-Garcia, Masako Narita, Yi Shen, Yangteng Ou, Zenon Toprakcioglu, Masashi Narita, Tuomas P. J. Knowles
Summary: This study reports a versatile microfluidic platform for generating biocompatible core-shell microgels with uniform cancer spheroids. In addition, an in situ micromechanics measuring device was used to determine the stiffness of individual artificial cancer niches. The power of the microfluidics-based method in modeling the interactions of stromal cancer cells with MCS-laden microgels is demonstrated.
ADVANCED NANOBIOMED RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Mario K. Shammas, Tzu-Hsiang Huang, Derek P. Narendra
Summary: Dominant mutations in CHCHD10 and its paralog CHCHD2 have been identified to be associated with familial ALS and PD, respectively, with phenotypes resembling the idiopathic forms of the diseases. These mutations also cause other neuromuscular disorders such as SMAJ and IMMD. Modeling these disorders has revealed the role of mitochondrial dysfunction and protein misfolding in ALS and PD pathogenesis, and provided insights for precision therapy. This review discusses the normal function of CHCHD2 and CHCHD10, their disease mechanisms, genotype-phenotype correlations, and potential therapeutic strategies.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2023)
Editorial Material
Biochemistry & Molecular Biology
Darren J. Baker, Masashi Narita, Pura Munoz-Canoves
Summary: The contribution of cellular senescence in various biological processes has been overlooked but is now gaining attention. This Editorial provides an overview of the review and original work articles in The FEBS Journal's Special Issue on Senescence in Ageing and Disease. Senescent cells have both positive and negative effects on tissue injury, aging, and pathology. The identification of senescent cells has improved, especially in slow-proliferating or terminally differentiated tissues. The communication between senescent cells and other tissue residents, as well as the role of the senescence-associated secretory phenotype (SASP), are important topics in this Special Issue.
Article
Cell Biology
Kosuke Tomimatsu, Dora Bihary, Ioana Olan, Aled J. Parry, Stefan Schoenfelder, Adelyne S. L. Chan, Guy St. C. Slater, Yoko Ito, Peter J. Rugg-Gunn, Kristina Kirschner, Camino Bermejo-Rodriguez, Tomomi Seko, Hiroyuki Kugoh, Ken Shiraishi, Koji Sayama, Hiroshi Kimura, Peter Fraser, Masako Narita, Shamith A. Samarajiwa, Masashi Narita
Summary: In this study, the authors found that some lineage-inappropriate genes are derepressed in senescent cells through physical decompaction of H3K9me3-heterochromatic regions.
Article
Medicine, Research & Experimental
Mario K. Shammas, Xiaoping Huang, Beverly P. Wu, Evelyn Fessler, Insung Y. Song, Nicholas P. Randolph, Yan Li, Christopher K. E. Bleck, Danielle A. Springer, Carl Fratter, Ines A. Barbosa, Andrew F. Powers, Pedro M. Quiros, Carlos Lopez-Otin, Lucas T. Jae, Joanna Poulton, Derek P. Narendra
Summary: Mitochondrial stress triggers responses in both cellular mitochondria and nucleus. This study focuses on the impact of a mutation in the mitochondrial protein CHCHD10, which causes myopathy. The study finds that the mutated CHCHD10 aggregates in affected tissues, causing toxic stress on the inner mitochondrial membrane. The research also reveals the crucial role of the mitochondrial metalloendopeptidase OMA1 in coordinating stress responses and reshaping the mitochondrial network and proteome.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
