Article
Multidisciplinary Sciences
Canbin Zheng, Yingying Hu, Masahiro Sakurai, Carlos A. Pinzon-Arteaga, Jie Li, Yulei Wei, Daiji Okamura, Benjamin Ravaux, Haley Rose Barlow, Leqian Yu, Hai-Xi Sun, Elizabeth H. Chen, Ying Gu, Jun Wu
Summary: Cell competition is a fitness-sensing process where fitter cells eliminate less-fit but viable cells. The study developed an interspecies PSC co-culture strategy and identified a previously unknown mode of cell competition between species. Genetic inactivation of key components of the NF-kappa B complex in human cells improved the survival and chimerism of human cells in early mouse embryos.
Review
Cell & Tissue Engineering
Gregg L. Semenza
Summary: Many advanced human cancers contain regions of intratumoral hypoxia which leads to the activation of HIFs and drives tumor growth and metastasis. Hypoxia induces the formation of breast cancer stem cells and affects the expression of pluripotency factors through various molecular mechanisms involving PLXNB3, NARF, and TERT. These findings provide important insights into the relationship between hypoxia and tumor progression.
STEM CELLS TRANSLATIONAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Shasha Li, Hui Liu, Weidong Liu, Ning Shi, Ming Zhao, Siyi Wanggou, Weiren Luo, Lei Wang, Bin Zhu, Xiang Zuo, Wen Xie, Cong Zhao, Yao Zhou, Longlong Luo, Xiang Gao, Xingjun Jiang, Caiping Ren
Summary: This study identified the functional role of the long noncoding RNA (lncRNA) ESRG, which is highly expressed in human pluripotent stem cells (hPSCs). The transcription of ESRG is directly regulated by the key self-renewal factor OCT4, and ESRG binds to the replication-licensing factor MCM2 to maintain its steady-state level and nuclear location. This protects against DNA replication errors and suppresses the activation of the p53 pathway, ultimately maintaining the self-renewal and pluripotency of hPSCs. These findings provide critical insights into the mechanisms underlying self-renewal and pluripotency maintenance in hPSCs by lncRNAs.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Mikhail L. Vorobev, Bashar A. Alhasan, Irina I. Suvorova
Summary: Autophagy plays a critical role in early embryonic development, particularly in blastocyst formation. The absence of p53 does not affect autophagy activation in pluripotent cells but hinders differentiation induced by retinoic acid. Despite p53 deletion, Ulk1-dependent autophagy is still activated in response to serum deprivation in mESCs, but impaired during differentiation induced by retinoic acid.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Review
Cell Biology
Coral K. Wille, Rupa Sridharan
Summary: DOT1-Like (DOT1L) is a methyltransferase that plays pleiotropic roles in cell development and differentiation. It is the sole methyltransferase of histone H3K79, a modification enriched on actively transcribing gene bodies. Loss of DOT1L activity results in upregulation of genes, contrary to the expected role of a modification associated with active transcription. DOT1L knockout leads to embryonic lethality. DOT1L also participates in cell type and developmental stage-specific epigenetic networks.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Cell Biology
Sarah W. Cai, Titia de Lange
Summary: In this review, the authors discuss the role of the CST-Polα/Primase complex in telomere length regulation. They highlight that this complex not only functions in strand synthesis but also controls telomerase to maintain telomere length. Additionally, they emphasize the importance of this complex in preventing telomeric disorders by replenishing lost sequences and determining telomere length.
GENES & DEVELOPMENT
(2023)
Article
Cell Biology
Daniel I. Sullivan, Fiona M. Bello, Agustin Gil Silva, Kevin M. Redding, Luca Giordano, Angela M. Hinchie, Kelly E. Loughridge, Ana L. Mora, Melanie Konigshoff, Brett A. Kaufman, Michael J. Jurczak, Jonathan K. Alder
Summary: Mitochondria play important roles in cellular metabolism and signaling. Defects in mitochondria caused by genetic or acquired factors can lead to various pathologies, including premature cellular senescence. In this study, we investigated the effects of dysfunctional telomeres on mitochondrial biogenesis and function during senescence. Our results showed that senescent cells had increased mitochondrial respiratory capacity and volume. Even in vivo, hepatocytes with dysfunctional telomeres maintained their mitochondrial respiratory capacity. The upregulation of genes related to mitochondria was observed during senescence in fibroblasts and hepatocytes. These findings suggest that mitochondrial function and activity are preserved in telomere dysfunction-induced senescence.
Article
Biochemistry & Molecular Biology
Hugo Martin, Marie Doumic, Maria Teresa Teixeira, Zhou Xu
Summary: This study provides a mathematical description of the generation-dependent processes underlying non-terminal arrests in telomerase-negative cells. The research highlights differences in the mechanisms and states between non-terminal and terminal senescence arrests. The findings suggest that these two processes contribute to different consequences of senescence at the population level.
CELL AND BIOSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Muhammad Azizan Samad, Mohd Zuwairi Saiman, Nazia Abdul Majid, Saiful Anuar Karsani, Jamilah Syafawati Yaacob
Summary: This study found that berberine can decrease telomerase activity and level in HCT 116 cells, which subsequently inhibits the proliferative ability of the cells.
Article
Multidisciplinary Sciences
Natthakan Thongon, Feiyang Ma, Andrea Santoni, Matteo Marchesini, Elena Fiorini, Ashley Rose, Vera Adema, Irene Ganan-Gomez, Emma M. Groarke, Fernanda Gutierrez-Rodrigues, Shuaitong Chen, Pamela Lockyer, Sarah Schneider, Carlos Bueso-Ramos, Guillermo Montalban-Bravo, Caleb A. Class, Kelly A. Soltysiak, Matteo Pellegrini, Ergun Sahin, Alison A. Bertuch, Courtney D. DiNardo, Guillermo Garcia-Manero, Neal S. Young, Karen Dwyer, Simona Colla
Summary: The study reveals that telomere attrition leads hematopoietic stem cells towards differentiation into megakaryocytic lineage through upregulated innate immune signaling response, ultimately compromising their self-renewal capabilities and leading to depletion. Targeting the IFI16 signaling axis could potentially prevent functional decline of hematopoietic stem cells under conditions affecting telomere maintenance.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Nela Pilbauerova, Tomas Soukup, Tereza Suchankova Kleplova, Jan Schmidt, Jakub Suchanek
Summary: Telomere length in dental pulp stem cells decreases with cultivation passaging, indicating that excessive proliferation leads to telomere attrition and affects cell proliferation capacity. However, prolongation of telomeres can be observed when cells are cultivated without passaging, suggesting that telomerase may be more efficient in this circumstance.
Review
Cell Biology
Puja Agrawal, Sridhar Rao
Summary: Cell fate decisions rely on gene expression changes mediated by regulatory elements like enhancers and CTCF binding sites. These elements play crucial roles in early mammalian development and impact cell-type specific gene expression.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Cell Biology
Yuanjie Ding, Yuanchun Yao, Xingmu Gong, Qi Zhuo, Jinhua Chen, Miao Tian, Maryam Farzaneh
Summary: JMJD3 is a key histone demethylase that regulates H3K27me3 and plays a crucial role in stem cell fate determination during the process of cell reprogramming.
CELL COMMUNICATION AND SIGNALING
(2021)
Review
Biochemistry & Molecular Biology
Semih Can Akincilar, Claire Hian Tzer Chan, Qin Feng Ng, Kerem Fidan, Vinay Tergaonkar
Summary: Telomerase activation is a common feature in cancer, but it does not directly correlate with telomere length. Aberrant expression of shelterin proteins and their release from shortened telomeres can further promote cancer through non-canonical mechanisms.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Rowan M. Karvas, Laurent David, Thorold W. Theunissen
Summary: Trophoblasts play critical roles in blastocyst implantation and maternal-fetal communication during pregnancy. However, our understanding of human trophoblast biology is limited due to the scarcity of first-trimester placental tissue and the inadequacy of animal models. Recent advancements in deriving human trophoblast stem cells from pluripotent and somatic cell sources provide exciting opportunities to study the molecular mechanisms of placental development and pregnancy-related diseases.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Omkar Suhas Vinchure, Kurt Whittemore, Deependra Kushwah, Maria A. Blasco, Ritu Kulshreshtha
Summary: miR-490 targets multiple genes to regulate telomere maintenance in GBM, exerting tumor suppressive effects, impacting stemness and senescence, activating DNA damage response, and potentially holding therapeutic significance in GBM treatment.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Cell Biology
Raul Sanchez-Vazquez, Ana Guio-Carrion, Antonio Zapatero-Gaviria, Paula Martinez, Maria A. Blasco
Summary: Shorter telomeres are associated with increased severity of COVID-19, particularly in older patients. This suggests that molecular pathways related to aging play a role in the disease's progression.
Article
Genetics & Heredity
Raul Sanchez-Vazquez, Paula Martinez, Maria A. Blasco
Summary: This study demonstrates how extracellular signals can regulate telomere protection and length through modifications in TRF1 protein. Mutations in TRF1 lead to decreased telomere binding, increased DNA damage, accelerated telomere shortening, impaired response to proliferative signals, and decreased tumorigenesis potential. It highlights the role of PI3K/AKT pathway in regulating telomere maintenance and suggests potential targets for cancer therapy.
Article
Cell Biology
Sergio Pineiro-Hermida, Paula Martinez, Maria A. Blasco
Summary: The study suggests that short or dysfunctional telomeres play a protective role in murine asthma by reducing airway hyperresponsiveness and mucus secretion following exposure to allergens.
Article
Geriatrics & Gerontology
Maria Giulia Bacalini, Anna Reale, Marco Malavolta, Fabio Ciccarone, Maria Moreno-Villanueva, Martijn E. T. Dolle, Eugene Jansen, Tilman Grune, Efstathios S. Gonos, Christiane Schoen, Juergen Bernhardt, Beatrix Grubeck-Loebenstein, Ewa Sikora, Olivier Toussaint, Florence Debacq-Chainiaux, Miriam Capri, Antti Hervonen, Mikko Hurme, P. Eline Slagboom, Nicolle Breusing, Valentina Aversano, Stefano Tagliatesta, Claudio Franceschi, Maria A. Blasco, Alexander Buerkle, Paola Caiafa, Michele Zampieri
Summary: The study found that changes in subtelomeric DNA methylation correlate with ageing progression, with linear changes observed in the general population, slower changes in the offspring of centenarians, and accelerated changes in Down syndrome individuals. These findings suggest that subtelomeric DNA methylation changes are a typical sign of ageing. Additionally, the effects of age on subtelomeric DNA methylation are mostly independent of other variables evaluated, including demographics and dietary/health habits.
Article
Oncology
Maria Monteagudo, Paula Martinez, Luis J. Leandro-Garcia, Angel M. Martinez-Montes, Bruna Calsina, Marta Pulgarin-Alfaro, Alberto Diaz-Talavera, Sara Mellid, Rocio Leton, Eduardo Gil, Manuel Perez-Martinez, Diego Megias, Raul Torres-Ruiz, Sandra Rodriguez-Perales, Patricia Gonzalez, Eduardo Caleiras, Scherezade Jimenez-Villa, Giovanna Roncador, Cristina Alvarez-Escola, Rita M. Regojo, Maria Calatayud, Sonsoles Guadalix, Maria Curras-Freixes, Elena Rapizzi, Letizia Canu, Svenja Noelting, Hanna Remde, Martin Fassnacht, Nicole Bechmann, Graeme Eisenhofer, Massimo Mannelli, Felix Beuschlein, Marcus Quinkler, Cristina Rodriguez-Antona, Alberto Cascon, Maria A. Blasco, Cristina Montero-Conde, Mercedes Robledo
Summary: Recent studies have highlighted the importance of telomere maintenance mechanisms involving TERT and ATRX genes in metastatic pheochromocytoma and paraganglioma (mPPGL). In addition to validating the predictive value of TERT and ATRX in mPPGL progression, this study also identified NOP10 as a novel prognostic risk marker of mPPGLs. By analyzing 29 telomere-related genes, it was found that NOP10 plays a role in telomerase-dependent telomere length maintenance in these tumors, suggesting its potential as a new marker for identifying metastatic-risk patients. The proposal to implement NOP10 immunohistochemistry (IHC) as part of the current marker panel for PPGL patients aims to improve clinical diagnoses.
Article
Cell Biology
Giuseppe Bosso, Pablo Lanuza-Gracia, Sergio Pineiro-Hermida, Merve Yilmaz, Rosa Serrano, Maria A. Blasco
Summary: BRAF(V600E) mutation is common in cancer and its expression leads to DNA damage response, inflammation, and differential changes in cell cycle and senescence-associated proteins in lung epithelia.
CELL DEATH & DISEASE
(2022)
Review
Biochemistry & Molecular Biology
Miriam Ayora, David Fraguas, Renzo Abregu-Crespo, Sandra Recio, Maria A. Blasco, Ana Moises, Aksinya Derevyanko, Celso Arango, Covadonga M. Diaz-Caneja
Summary: The meta-analysis found that leukocyte telomere length was significantly shorter in patients with schizophrenia and related disorders compared to healthy controls, with no significant effects of age or illness duration on this difference. The results support the hypothesis of accelerated cellular aging in schizophrenia and related disorders, highlighting the need for large longitudinal studies with repeated telomere length measurements and appropriate assessments of associated factors.
MOLECULAR PSYCHIATRY
(2022)
Article
Genetics & Heredity
Paula Martinez, Raul Sanchez-Vazquez, Iole Ferrara-Romeo, Rosa Serrano, Juana M. Flores, Maria A. Blasco
Summary: By generating a mouse model for the human POT1(R117C) mutation, this study found that the mutation leads to longer telomeres and exerts dominant-negative effects at telomeres. Heterozygous mice with this mutation also develop angiosarcomas, including cardiac angiosarcomas. This research provides important insights into human cancers initiated by POT1 mutations.
Article
Multidisciplinary Sciences
Sergio Pineiro-Hermida, Paula Martinez, Giuseppe Bosso, Juana Maria Flores, Sarita Saraswati, Jane Connor, Raphael Lemaire, Maria A. Blasco
Summary: Depletion of TRF1 does not lead to interstitial lung fibrosis, highlighting the relevance of alveolar type II cells in this disease.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Jorge Sanz-Ros, Nekane Romero-Garcia, Cristina Mas-Bargues, Daniel Monleon, Juozas Gordevicius, Robert T. Brooke, Mar Dromant, Ana Diaz, Aksinya Derevyanko, Ana Guio-Carrion, Aurora Roman-Dominguez, Marta Ingles, Maria A. Blasco, Steve Horvath, Jose Vina, Consuelo Borras
Summary: This study found that treatment of old animals with ADSC-sEVs derived from young animals can improve various parameters associated with aging and reduce frailty. This treatment induces proregenerative effects and reduces oxidative stress, inflammation, and senescence in muscle and kidney. Additionally, tissue epigenetic age decreases and metabolome shifts to a youth-like pattern after this treatment.
Article
Oncology
Cristina Montero-Conde, Luis Javier Leandro-Garcia, Angel M. Martinez-Montes, Paula Martinez, Francisco J. Moya, Rocio Leton, Eduardo Gil, Natalia Martinez-Puente, Sonsoles Guadalix, Maria Curras-Freixes, Laura Garcia-Tobar, Carles Zafon, Mireia Jorda, Garcilaso Riesco-Eizaguirre, Patricia Gonzalez-Garcia, Maria Monteagudo, Rafael Torres-Perez, Veronika Mancikova, Sergio Ruiz-Llorente, Manuel Perez-Martinez, Guillermo Pita, Juan Carlos Galofre, Anna Gonzalez-Neira, Alberto Cascon, Cristina Rodriguez-Antona, Diego Megias, Maria A. Blasco, Eduardo Caleiras, Sandra Rodriguez-Perales, Mercedes Robledo
Summary: Comprehensive molecular studies were conducted on thyroid tumors to identify prognostic biomarkers. Telomere-related alterations, especially TERT and TERC, were found in aggressive tumors. Short telomeres led to reorganization in the 5p subtelomeric region, resulting in increased gene upregulation and a more relaxed chromatin configuration in the tumors.
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
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
Biochemistry & Molecular Biology
Sergio Pineiro-Hermida, Giuseppe Bosso, Raul Sanchez-Vazquez, Paula Martinez, Maria A. Blasco
Summary: Non-small cell lung cancer (NSCLC) is a leading cause of cancer death, and tumor progression is influenced by the interaction between cancer cells and the tumor microenvironment. Increased copy number and mRNA expression of TERT, a catalytic subunit of telomerase, is associated with decreased survival in NSCLC patients. Targeting telomeres may be an effective therapeutic approach in NSCLC treatment.
CELL DEATH AND DIFFERENTIATION
(2023)
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.
