Article
Multidisciplinary Sciences
Marta Markiewicz-Potoczny, Anastasia Lobanova, Anisha M. Loeb, Oktay Kirak, Teresa Olbrich, Sergio Ruiz, Eros Lazzerini Denchi
Summary: The loss of TRF2 in mouse embryonic stem cells triggers a compensatory transcriptional program that renders TRF2 dispensable for cell survival and proliferation. The unique DNA damage response in TRF2-null ES cells is controlled by telomere-associated protein POT1B and chromatin remodelling factor BRD2, and is characterized by the upregulation of ZSCAN4.
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.
Review
Biochemistry & Molecular Biology
Ping Zheng
Summary: Pluripotent stem cells have wide applications, but the mechanisms of maintaining genome stability in these cells are not clear.
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
(2022)
Article
Cell Biology
Hayley Robinson, Sk Imran Ali, Martha Elena Diaz-Hernandez, Rodrigo Lopez-Gonzalez
Summary: The G4C2 repeat expansion in C9ORF72 gene is the most common genetic cause of ALS and FTD. This study found an age-dependent decrease in telomere length in neurons from C9ORF72 carriers, along with dysregulation in the protein levels of shelterin complex members TRF2 and POT1.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Biotechnology & Applied Microbiology
Wei Cheng, Chengming Fan, Qing Song, Ping Chen, Hong Peng, Ling Lin, Cong Liu, Bin Wang, Zijing Zhou
Summary: Fibrotic diseases are responsible for a third of global deaths, leading to organ remodeling and dysfunction. Despite the complications of organ transplantation, induced pluripotent stem cell (iPSC)-based therapy shows potential as a treatment option by replacing fibrotic organs. Recent studies have successfully differentiated iPSCs into fibrosis-relevant cell types with anti-fibrotic effects, providing promising precision treatments for organ-specific fibrosis. This review summarizes the potential, advantages, challenges, and future outlook of iPSC-based approaches in treating organ fibrosis.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Article
Multidisciplinary Sciences
Bruno Silva, Rajika Arora, Silvia Bione, Claus M. Azzalin
Summary: TERRA transcription actively destabilizes telomere integrity in ALT cells, thereby triggering BIR and promoting telomere elongation.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Ying Zhang, Jun Wei, Jiani Cao, Kehua Zhang, Yaojin Peng, Hongkui Deng, Jiuhong Kang, Guangjin Pan, Yong Zhang, Boqiang Fu, Shijun Hu, Jie Na, Yan Liu, Lei Wang, Lingmin Liang, Huanxin Zhu, Yu Zhang, Zi-Bing Jin, Jie Hao, Aijin Ma, Tongbiao Zhao, Junying Yu
Summary: "Requirements for Human-Induced Pluripotent Stem Cells" is the first set of guidelines in China on human-induced pluripotent stem cells. It provides detailed technical requirements and aims to promote international standardization.
CELL PROLIFERATION
(2022)
Review
Biochemistry & Molecular Biology
Tianyuan Shi, Martin Cheung
Summary: Using rodents for modeling neurological diseases has limitations due to differences in genetics, neural development, and physiology between humans and rodents. In the past decade, induced pluripotent stem cells and induced neural stem cells generated through reprogramming somatic cells have offered a powerful alternative for studying disease pathogenesis and testing regenerative medicines. Urine-derived stem cells are an ideal cell source for reprogramming due to their proliferation, multipotency, epithelial nature, and ease of reprogramming.
CELL AND BIOSCIENCE
(2021)
Article
Peripheral Vascular Disease
Lu Liu, Charlene Jouve, Josephine Henry, Takiy-Eddine Berrandou, Jean-Sebastien Hulot, Adrien Georges, Nabila Bouatia-Naji
Summary: This study characterized the cellular phenotypes, epigenomic and proteomic profiles of smooth muscle cells (SMCs) derived from induced pluripotent stem cells (iPSCs) and evaluated their potential as cellular models for complex diseases. The iPSC-derived SMCs demonstrated different functional properties and gene expression profiles. These cellular models have the potential to investigate the functional regulation of genetic risk loci in major arterial diseases.
Review
Cell Biology
Samantha E. Spellicy, David C. Hess
Summary: Inflammation is a key contributing factor to the pathogenesis of stroke, leading to increased oxidative stress and neuronal cell death. Recent research has shown that induced pluripotent stem cells have the potential to suppress neuroinflammation, mainly by modulating inflammatory signaling and endogenous inflammatory cell populations.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Shihori Yokobayashi, Yukihiro Yabuta, Masato Nakagawa, Keisuke Okita, Bo Hu, Yusuke Murase, Tomonori Nakamura, Guillaume Bourque, Jacek Majewski, Takuya Yamamoto, Mitinori Saitou
Summary: The research demonstrates significant epigenomic heterogeneity in hiPSCs, with different germline potential correlating with X chromosome inactivation. This heterogeneity is primarily determined by genomic properties.
Article
Biochemistry & Molecular Biology
Ronghuan Ji, Xinying Xu, Jun Liu, Tao Zhao, Hongyu Li, Jixian Zhai, Bin Liu
Summary: In this study, the roles of two COP1 homologous genes, GmCOP1a and GmCOP1b, were investigated in soybean. It was found that GmCOP1b plays a more prominent role in promoting stem elongation under normal light conditions. Additionally, GmCOP1b mutants exhibited reduced shade response and performed better under high-density conditions in field trials.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Dwaipayan Adhya, Vivek Swarup, Roland Nagy, Lucia Dutan, Carole Shum, Eva P. Valencia-Alarcon, Kamila Maria Jozwik, Maria Andreina Mendez, Jamie Horder, Eva Loth, Paulina Nowosiad, Irene Lee, David Skuse, Frances A. Flinter, Declan Murphy, Grainne McAlonan, Daniel H. Geschwind, Jack Price, Jason Carroll, Deepak P. Srivastava, Simon Baron-Cohen
Summary: The study suggests that autism-iPSCs diverge from control-iPSCs at a cellular level during early neurodevelopment, indicating unique developmental differences associated with autism may be established at early prenatal stages.
BIOLOGICAL PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Yue Su, Ling Wang, Zhiqiang Fan, Ying Liu, Jiaqi Zhu, Deborah Kaback, Julia Oudiz, Tayler Patrick, Siu Pok Yee, Xiuchun (Cindy) Tian, Irina Polejaeva, Young Tang
Summary: This study successfully generated biPSCs with long-term self-renewal capacity and pluripotent characteristics from bovine mesenchymal stem cells. The cells exhibited morphological changes under different culture conditions, and transcriptome analysis showed high similarity to bovine ESCs and embryos. The naive-like biPSCs also demonstrated the ability to integrate into extra-embryonic tissues.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Yong-Jin Kim, Amin Tamadon, Yoon-Young Kim, Byeong-Cheol Kang, Seung-Yup Ku
Summary: This review focuses on the current knowledge of epigenetic regulation of cardiomyocyte proliferation and differentiation from embryonic and induced pluripotent stem cells through histone modification and microRNAs, the maintenance of pluripotency, and its alteration during cardiac lineage differentiation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
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
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.
Editorial Material
Chemistry, Physical
Paula Martinez, Maria A. Blasco
Summary: Telomerase, discovered over 35 years ago by Elizabeth H. Blackburn and Carol W. Greider, is now seen as a promising approach to curing some age-related diseases and cancer. However, it took time for telomerase to be recognized and become in the spotlight.
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.
Article
Cell Biology
Sarita Saraswati, Paula Martinez, Osvaldo Grana-Castro, Maria A. Blasco
Summary: Accumulation of short telomeres is a hallmark of aging and can sensitize kidneys to develop fibrosis by influencing the EMT program. Deletion of Trf1 in kidneys also leads to fibrosis and EMT activation. This study shows that short and dysfunctional telomeres enhance the genetic program associated with epithelial-to-mesenchymal transition in two mouse models of kidney fibrosis.