Review
Biochemistry & Molecular Biology
Lina-Marie Briu, Chrystelle Maric, Jean-Charles Cadoret
Summary: The replication-timing program is crucial in eukaryotic nuclear processes and is closely linked to transcriptional activity, epigenetic landscape, and the 3D organization of the genome. There is a complex relationship between replication timing, replication stress, and genomic instability, although the extent of their mutual connection requires further investigation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Hyun Kyu Kim, Tae Won Ha, Man Ryul Lee
Summary: Cells are the basic units of organisms, with over 30 trillion cells generated from a single-cell fertilized egg through division and differentiation. Establishing the Human Cell Atlas aims to understand the mechanisms underlying diseases and cellular activities.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell & Tissue Engineering
Shijia Liuyang, Guan Wang, Yanglu Wang, Huanjing He, Yulin Lyu, Lin Cheng, Zhihan Yang, Jingyang Guan, Yao Fu, Jialiang Zhu, Xinxing Zhong, Shicheng Sun, Cheng Li, Jinlin Wang, Hongkui Deng
Summary: We have developed a robust and chemically defined reprogramming protocol that significantly shortens the induction time for generating human pluripotent stem cells from somatic cells. This protocol promotes cell proliferation and metabolic activities, leading to a more direct reprogramming process.
Review
Cell Biology
Rafaela Fagundes, Leonardo K. Teixeira
Summary: DNA replication must be precisely controlled, and cell cycle transitions are regulated by the Cyclin-Dependent Kinases (CDKs) family. The Cyclin E/CDK2 complex controls cell cycle progression and DNA replication through phosphorylation of specific substrates in normal cycles, while its oncogenic activation causes replication stress and genomic instability.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biology
Yoichiro Harada, Yu Mizote, Takehiro Suzuki, Akiyoshi Hirayama, Satsuki Ikeda, Mikako Nishida, Toru Hiratsuka, Ayaka Ueda, Yusuke Imagawa, Kento Maeda, Yuki Ohkawa, Junko Murai, Hudson H. Freeze, Eiji Miyoshi, Shigeki Higashiyama, Heiichiro Udono, Naoshi Dohmae, Hideaki Tahara, Naoyuki Taniguchi
Summary: Mannose has anticancer activity by regulating cell metabolism and inducing dNTP loss, affecting cell cycle and chemotherapy efficacy.
Article
Cell & Tissue Engineering
Wei-Fang Chang, Tzu-Ying Lin, Min Peng, Chia-Chun Chang, Jie Xu, Hsiu-Mei Hsieh-Li, Ji-Long Liu, Li-Ying Sung
Summary: SMN is shown to play a crucial role in cell reprogramming, as its overexpression increases iPSC formation efficiency and restores differentiation capacity of SMA-iPSCs.
STEM CELLS AND DEVELOPMENT
(2022)
Review
Biochemistry & Molecular Biology
Veronica Marabitti, Pasquale Valenzisi, Giorgia Lillo, Eva Malacaria, Valentina Palermo, Pietro Pichierri, Annapaola Franchitto
Summary: Maintenance of genome stability is crucial for cell survival, which relies on accurate DNA replication. Transcription poses as a major threat to DNA replication, as collisions between the two processes occur frequently. R-loops, which consist of a DNA-RNA hybrid and displaced single-stranded DNA, are the main harmful structures associated with transcription. When their homeostasis is disturbed, R-loops become a potent source of replication stress and genome instability, leading to various human diseases including cancer. Cells have evolved multiple mechanisms to combat the deleterious consequences of R-loop persistence, and several replication fork protection factors have been implicated in preventing/removing these harmful structures.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Niccolo Liorni, Alessandro Napoli, Stefano Castellana, Sebastiano Giallongo, Daniela Rehakova, Oriana Lo Re, Irena Koutna, Tommaso Mazza, Manlio Vinciguerra
Summary: This study used a combination of CUT&Tag and RNA-Seq data to analyze the differences between macroH2A1.1 and macroH2A1.2 during iPSCs reprogramming. The results demonstrated that macroH2A1.1 had wider genome occupancy and specifically activated ectoderm/neural processes during reprogramming.
Review
Cell & Tissue Engineering
Mareike S. Poetsch, Anna Strano, Kaomei Guan
Summary: The potential of human-induced pluripotent stem cells (iPSCs) in various fields such as disease modeling, drug screening, personalized medicine, and regenerative therapies is attractive. However, the genetic integrity and epigenetic memory of iPSCs can affect their application.
Article
Multidisciplinary Sciences
Ke Zhang, Yang Sui, Wu-Long Li, Gen Chen, Xue-Chang Wu, Robert J. Kokoska, Thomas D. Petes, Dao-Qiong Zheng
Summary: The deficiency of Pol epsilon leads to genomic instability and multiple human diseases. Low levels of Pol epsilon result in cellular changes such as elevated rates of recombination, aneuploidy, contraction of ribosomal DNA repeats, shortened telomeres, increased break-induced replication, and higher rate of single-base mutations. Compared to other replicative DNA polymerases, Pol epsilon displays distinct patterns of genomic alterations.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Oncology
Akira Fujimori, Hirokazu Hirakawa, Cuihua Liu, Taishin Akiyama, Bevin P. Engelward, Jac A. Nickoloff, Masao Suzuki, Bing Wang, Mitsuru Nenoi, Sei Sai
Summary: This study aimed to investigate the role of homologous recombination (HR)-related genomic instability in ionizing radiation-induced thymic lymphoma in mice. The results showed that ionizing radiation induced genome instability, leading to the development of thymic lymphoma.
AMERICAN JOURNAL OF CANCER RESEARCH
(2022)
Review
Endocrinology & Metabolism
Ila Tewari Jasra, Nerea Cuesta-Gomez, Kevin Verhoeff, Braulio A. Marfil-Garza, Nidheesh Dadheech, A. M. James Shapiro
Summary: This review summarizes the roles and mechanisms of mitochondria in somatic cell reprogramming to iPSCs and the metabolic shift associated with directed differentiation into pancreatic beta-like cells.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Deogil Kim, Byung-Hyun Cha, Jinsung Ahn, Yoshie Arai, Bogyu Choi, Soo-Hong Lee
Summary: Understanding the biophysical relationships between stem cells and applied biomaterials is crucial in controlling stem cell functions. This study highlights the significant role of 3D microenvironment, particularly methacrylated hyaluronic acid (HA) hydrogel, in improving cellular reprogramming into iPSCs. The incorporation of cues from the 3D microenvironment accelerates the reprogramming process, offering potential advantages for translational applications.
ADVANCED FUNCTIONAL MATERIALS
(2021)
Article
Genetics & Heredity
Huajin Li, Wenting Xu, Sijia Xiang, Leiting Tao, Wen Fu, Jinhui Liu, Wenbin Liu, Yamei Xiao, Liangyue Peng
Summary: Pluripotency is a transient state in early embryos regulated by a network of pluripotency-related genes. This study identified four pluripotent genes in zebrafish and crucian carp and verified that three of them can be used as markers for pluripotency in induced pluripotent stem cells in fish.
FRONTIERS IN GENETICS
(2022)
Article
Multidisciplinary Sciences
Harald Vohringer, Arne Van Hoeck, Edwin Cuppen, Moritz Gerstung
Summary: TensorSignatures algorithm can learn mutational signatures across different variant categories and their genomic properties. By analyzing multiple genomic variables, it elucidates complex mutational footprints and their underlying processes.
NATURE COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Alba Corman, Oleksandra Sirozh, Vanesa Lafarga, Oscar Fernandez-Capetillo
Summary: The nucleolus is where ribosome biogenesis takes place, which is one of the most resource-intensive processes in eukaryotic cells. It is highly responsive to growth signaling and nucleolar insults, collectively known as nucleolar stress. Nucleolar alterations are a prominent feature in various human diseases, including cancer and neurodegeneration, and are also associated with aging. There have been numerous efforts to develop compounds targeting different aspects of nucleolar activity. This article provides an overview of therapeutic opportunities and current therapies for targeting nucleoli in different pathologies.
TRENDS IN BIOCHEMICAL SCIENCES
(2023)
Article
Oncology
Ines Marin, Olga Boix, Andrea Garcia-Garijo, Isabelle Sirois, Adria Caballe, Eduardo Zarzuela, Irene Ruano, Camille Stephan-Otto Attolini, Neus Prats, Jose A. Lopez-Dominguez, Marta Kovatcheva, Elena Garralda, Javier Munoz, Etienne Caron, Maria Abad, Alena Gros, Federico Pietrocola, Manuel Serrano
Summary: Senescent cells possess various features that make them highly efficient in stimulating dendritic cells and antigen-specific CD8 T cells, including the release of alarmins, activation of IFN signaling, enhanced MHC class I machinery, and presentation of specific self-peptides. Immunization with senescent cancer cells induces strong antitumor protection mediated by DCs and CD8 T cells, surpassing the effectiveness of immunization with cancer cells undergoing immunogenic cell death. Furthermore, induction of senescence in human primary cancer cells enhances their ability to activate autologous antigen-specific tumor-infiltrating CD8 lymphocytes. This study highlights the potential of exploiting senescent cancer cells to develop efficient and protective CD8-dependent antitumor immune responses.
Article
Pathology
Thiebaud Picart, Delphine Poncet, Marc Barritault, Luc Bauchet, Sonia Zouaoui, Jacques Guyotat, Mathieu Gabut, Frederic Fina, Jerome Honnorat, Dominique Figarella-Branger, Johan Pallud, Francois Ducray, David Meyronet
Summary: The aim of this study was to identify subgroups of cerebellar glioblastoma (cGBM) based on targeted molecular analysis. Eighty-three cGBM cases were included and classified into 6 mutually exclusive subgroups associated with age at diagnosis and prognosis. MAPK pathway-activating alterations were found to be associated with a better outcome.
AMERICAN JOURNAL OF SURGICAL PATHOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Carlos Lopez-Otin, Maria A. Blasco, Linda Partridge, Manuel Serrano, Guido Kroemer
Summary: Aging is driven by hallmarks that manifest with age, accelerate aging when accentuated experimentally, and can be decelerated, stopped, or reversed with therapeutic interventions. The twelve proposed hallmarks of aging include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation, and dysbiosis. These hallmarks are interconnected with each other and with the recently proposed hallmarks of health.
Article
Chemistry, Multidisciplinary
Marcia Dominguez, Kathleen Meyer, Felix Sancenon, Juan F. Blandez, Manuel Serrano, Ramon Martinez-Manez
Summary: Kidney damage can be monitored using different biomarkers in blood, urine or serum, and kidney failure leads to the overexpression of the alanine aminopeptidase (APN) enzyme in urine. In this study, a molecular probe (NB-ALA) based on the Nile Blue fluorophore (NB) was designed to detect APN enzyme in urine through simple fluorometric measurements.
CHEMICAL COMMUNICATIONS
(2023)
Review
Genetics & Heredity
David Juan, Gabriel Santpere, Joanna L. Kelley, Omar E. Cornejo, Tomas Marques-Bonet
Summary: Primate genomics is crucial for understanding human evolution and disease. Currently, there is limited data available on genetic diversity and functional genomics of primate species. Efforts are being made to characterize primate genomes, genetic variation, and functional landscapes. These data sets will provide insights into the genetics of primate traits and human diseases. This review discusses existing genome assemblies, genetic variation, and challenges in sample acquisition. It also explores how technological advances in single-cell functional genomics and induced pluripotent stem cell-derived organoids will enhance our understanding of primate biology.
NATURE REVIEWS GENETICS
(2023)
Article
Multidisciplinary Sciences
Sebastien Durand, Marion Bruelle, Fleur Bourdelais, Bigitha Bennychen, Juliana Blin-Gonthier, Caroline Isaac, Aurelia Huyghe, Sylvie Martel, Antoine Seyve, Christophe Vanbelle, Annie Adrait, Yohann Coute, David Meyronet, Frederic Catez, Jean-Jacques Diaz, Fabrice Lavial, Emiliano P. Ricci, Francois Ducray, Mathieu Gabut
Summary: The study reveals that RSL24D1 is highly expressed in both mouse and human pluripotent stem cells and is involved in the biogenesis of 60S subunits. Depletion of RSL24D1 impairs global translation, particularly of pluripotency factors and components from the Polycomb Repressive Complex 2 (PRC2), leading to altered self-renewal and lineage commitment choices in embryonic stem cells.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Ines Marin, Manuel Serrano, Federico Pietrocola
Summary: Cancer therapy-induced senescence in cancer cells can interact with the immune system to enhance cancer surveillance and promote clearance of both senescent and non-senescent neoplastic cells. Recent studies have shown that senescent cancer cells have potent antigenicity and adjuvanticity and can induce strong CD8(+) T cell-dependent anticancer effects when used as vaccination agents.
Review
Pharmacology & Pharmacy
Margherita Protasoni, Manuel Serrano
Summary: Ageing is characterized by cellular dysfunction and overall deterioration of tissues and organs, making individuals more susceptible to diseases. This article examines the relationship between mitochondrial dysfunction and cellular senescence, two key factors in the ageing process. By targeting specific mitochondrial features in senescent cells, it may be possible to delay or reverse ageing. Understanding the alterations in mitochondrial function and structure, as well as available treatments, can pave the way for future anti-ageing therapies.
Review
Genetics & Heredity
Paula Aguilera, Andres J. Lopez-Contreras
Summary: ATRX is a frequently mutated tumor suppressor gene in human cancers, especially in glioma. Recent studies have revealed its important roles in key molecular pathways, such as the regulation of chromatin state, gene expression, and DNA damage repair, making it a central player in maintaining genome stability and function. This article provides an overview of ATRX interactions and molecular functions, as well as discussing the consequences of its impairment, including alternative lengthening of telomeres and therapeutic vulnerabilities in cancer cells.
TRENDS IN GENETICS
(2023)
Article
Anthropology
Ian Armit, Claire-Elise Fischer, Hannah Koon, Rebecca Nicholls, Inigo Olalde, Nadin Rohland, Jo Buckberry, Janet Montgomery, Philip Mason, Matija Cresnar, Lindsey Buster, David Reich
Summary: The results of aDNA and isotope analyses conducted on seven individuals from an Early Iron Age barrow in Slovenia suggest that all seven individuals are close biological relatives. The funerary tradition appears highly gendered, and family links through both the male and female lines seem important in structuring the community. These findings have implications for understanding kinship and funerary practices in late prehistoric Europe.
Article
Cell Biology
Paula Martinez, Raul Sanchez-Vazquez, Arpita Saha, Maria S. Rodriguez-Duque, Sara Naranjo-Gonzalo, Joy S. Osorio-Chavez, Ana V. Villar-Ramos, Maria A. Blasco
Summary: The severity of COVID-19 increases with age, suggesting that organismal aging contributes to its fatality. Previous studies have shown that COVID-19 severity is correlated with shorter telomeres in patient's leukocytes. Lung injury is a prominent feature of acute SARS-CoV-2 infection, which can progress to lung fibrosis. In this study, we found that post-COVID-19 patients have shorter telomeres and increased lung fibrosis compared to age-matched controls with lung cancer, suggesting a link between short telomeres in ATII cells and long-term lung fibrosis in post-COVID-19 patients.
Review
Oncology
Andreas Bikfalvi, Cristine Alves da Costa, Tony Avril, Jean-Vianney Barnier, Luc Bauchet, Lucie Brisson, Pierre Francois Cartron, Helene Castel, Eric Chevet, Herve Chneiweiss, Anne Clavreul, Bruno Constantin, Valerie Coronas, Thomas Daubon, Monique Dontenwill, Francois Ducray, Natacha Entz-Werle, Dominique Figarella-Branger, Isabelle Fournier, Jean-Sebastien Frenel, Mathieu Gabut, Thierry Galli, Julie Gavard, Gilles Huberfeld, Jean-Philippe Hugnot, Ahmed Idbaih, Marie-Pierre Junier, Thomas Mathivet, Philippe Menei, David Meyronet, Celine Mirjolet, Fabrice Morin, Jean Mosser, Elisabeth Cohen-Jonathan Moyal, Veronique Rousseau, Michel Salzet, Marc Sanson, Giorgio Seano, Emeline Tabouret, Aurelie Tchoghandjian, Laurent Turchi, Francois M. Vallette, Somya Vats, Maite Verreault, Thierry Virolle
Summary: Glioblastoma (GBM) is a highly lethal brain tumor, and recent studies have emphasized the importance of the tumor microenvironment (TME) as a therapeutic target. However, a comprehensive understanding of the different cellular and molecular components involved in the GBM TME and their interactions is still needed for the development of more effective treatments. This review presents a comprehensive report on the GBM TME, combining the contributions of researchers and physicians in France, and provides a holistic view of the subject by describing the specific features of the GBM TME at the cellular, molecular, and therapeutic levels.
Article
Geriatrics & Gerontology
Ines Marin, Manuel Serrano, Federico Pietrocola
Summary: Recent reports provide strong evidence that senescent cells undergo surveillance by CD8 T cell-mediated adaptive immunity in both oncological and non-oncological experimental setups. These findings also reveal the mechanisms of sensitizing senescent cells to CD8 T cell-dependent killing and the mechanisms of senescent cell evasion from CD8 T cell immunosurveillance. Understanding the interplay between cellular senescence and the adaptive immune system could potentially lead to new strategies for mitigating aging and aging-associated diseases.
Article
Biochemical Research Methods
Jaime Martinez de Villarreal, Mark Kalisz, Gabriel Piedrafita, Osvaldo Grana-Castro, Dafni Chondronasiou, Manuel Serrano, Francisco X. Real
Summary: Transposable elements have played a major role in shaping mammalian genomes, but little is known about their cell-type-specific expression. A cost-efficient single-cell-resolution TE expression analytical approach is needed.
