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206. Nuclear Genomic Instability and Aging

Author

Niedernhofer, Laura J., primary, Gurkar, Aditi U., additional, Wang, Yinsheng, additional, Vijg, Jan, additional, Hoeijmakers, Jan H.J., additional, and Robbins, Paul D., additional

Published
2018
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207. Global, integrated analysis of methylomes and transcriptomes from laser capture microdissected bronchial and alveolar cells in human lung

Author

Dong, Xiao, primary, Shi, Miao, additional, Lee, Moonsook, additional, Toro, Rafael, additional, Gravina, Silvia, additional, Han, Weiguo, additional, Yasuda, Shoya, additional, Wang, Tao, additional, Zhang, Zhengdong, additional, Vijg, Jan, additional, Suh, Yousin, additional, and Spivack, Simon D., additional

Published
2018
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208. Plasmid-based transgenic mouse model for studying in vivo mutations

Author

Boerrigter, Michael E.T.I., Dolle, Martijn E.T., Martus, Hans-Jorg, Gossen, Jan A., and Vijg, Jan

Subjects
Mutation (Biology) -- Research, Plasmids -- Usage, Mice as laboratory animals -- Observations, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

A method developed for studying somatic mutations involve separation of mouse plasmids containing the lacZ reporter gene by putting a restriction on enzyme digestion. These plasmids are then introduced into Escherichia coli cells. Cells containing galE mutation are viable as they do not contain the UDPgal 4-epimerase enzyme when the wild-life cells die. In this method the DNA fragment is easily separated as the plasmid vector is small. In plasmid separation the mutant lacZ genes are easily identified.

Published
1995

213. Development and validation of a targeted next generation DNA sequencing panel outperforming whole exome sequencing for the identification of clinically relevant genetic variants

Author

Miller, Eirwen M., primary, Patterson, Nicole E., additional, Zechmeister, Jenna Marcus, additional, Bejerano-Sagie, Michal, additional, Delio, Maria, additional, Patel, Kunjan, additional, Ravi, Nivedita, additional, Quispe-Tintaya, Wilber, additional, Maslov, Alexander, additional, Simmons, Nichelle, additional, Castaldi, Maria, additional, Vijg, Jan, additional, Karabakhtsian, Rouzan G., additional, Greally, John M., additional, Kuo, Dennis Y.S., additional, and Montagna, Cristina, additional

Published
2017
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223. Distinct spectra of somatic mutations accumulated with age in mouse heart and small intestine

Author

Dolle, Martijn E. T., Snyder, Wendy K., Gossen, Jan A., Lohman, Paul H. M., and Vijg, Jan

Subjects
Gene mutations -- Research, Genetically modified mice -- Genetic aspects, Cancer -- Genetic aspects, Aging -- Genetic aspects, Science and technology
Abstract

Somatic mutation accumulation has been implicated as a major cause of cancer and aging. By using a transgenic mouse model with a chromosomally integrated lacZ reporter gene, mutational spectra were characterized at young and old age in two organs greatly differing in proliferative activity, i.e., the heart and small intestine. At young age the spectra were nearly identical, mainly consisting of G [multiplied by] C to A [multiplied by] T transitions and 1-bp deletions. At old age, however, distinct patterns of mutations had developed. In small intestine, only point mutations were found to accumulate, including G [multiplied by] C to T [multiplied by] A, G [multiplied by] C to C [multiplied by] G, and A [multiplied by] T to C [multiplied by] G transversions and G [multiplied by] C to A [multiplied by] T transitions. In contrast, in heart about half of the accumulated mutations appeared to be large genome rearrangements, involving up to 34 centimorgans of chromosomal DNA. Virtually all other mutations accumulating in the heart appeared to be G [multiplied by] C to A [multiplied by] T transitions at CpG sites. These results suggest that distinct mechanisms lead to organ-specific genome deterioration and dysfunction at old age.

Published
2000

224. Additional file 8: Figure S2. of Comprehensive transcriptional landscape of aging mouse liver

Author

White, Ryan, Milholland, Brandon, MacRae, Sheila, Mingyan Lin, Deyou Zheng, and Vijg, Jan

Abstract

Representative subset (Meg3, Rian and Mirg) of maternally expressed and imprinted ncRNA locus, Dlk-Dio3, on chromosome 12 in UCSC Genome Browser overlaid with aligned reads from RNA-seq dataset. Blue = sense paired-end, red = antisense paired-end; Scale = 100 kb. (PDF 64 kb)

Published
2015
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225. Additional file 7: Figure S1. of Comprehensive transcriptional landscape of aging mouse liver

Author

White, Ryan, Milholland, Brandon, MacRae, Sheila, Mingyan Lin, Deyou Zheng, and Vijg, Jan

Abstract

RNAseq validation. (a) qPCR validation of 13 selected transcripts normalized to eukaryotic 18 s rRNA using TaqMan primer/probe sets. (b) qPCR validation of 13 differentially expressed non-coding RNAs normalized to GAPDH mRNA using custom made primer for each novel ncRNA. For both, RNA-seq and qPCR values are plotted as the mean (Old, n = 3; Young, n = 3) log2FoldChange(Old/Young) value, where the red line indicates the slope of linear regression and the square of Pearson’s correlation coefficient (r). Insets are bar plots of equivalent corresponding values. (PDF 122 kb)

Published
2015
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226. Controlled induction of DNA double-strand breaks in the mouse liver induces features of tissue ageing

Author

White, Ryan R, Milholland, Brandon, de Bruin, Alain, Curran, Samuel, Laberge, Remi-Martin, van Steeg, Harry, Campisi, Judith, Maslov, Alexander Y, Vijg, Jan, LS Pathobiologie, Tissue Repair, PB TR, Regenerative Medicine, Stem Cells & Cancer, LS Pathobiologie, Tissue Repair, PB TR, and Regenerative Medicine, Stem Cells & Cancer

Subjects
Male, Senescence, Aging, DNA Repair, DNA damage, DNA repair, Genetic Vectors, General Physics and Astronomy, Biology, medicine.disease_cause, Article, General Biochemistry, Genetics and Molecular Biology, Adenoviridae, Mice, chemistry.chemical_compound, medicine, Animals, DNA Breaks, Double-Stranded, Transgenes, Deoxyribonucleases, Type II Site-Specific, Regulation of gene expression, Mice, Inbred BALB C, Multidisciplinary, Gene Expression Profiling, DNA, General Chemistry, Tetracycline, Molecular biology, 3. Good health, Cell biology, Gene expression profiling, Gene Expression Regulation, Liver, chemistry, Ageing, Biomarkers
Abstract

DNA damage has been implicated in ageing, but direct evidence for a causal relationship is lacking, owing to the difficulty of inducing defined DNA lesions in cells and tissues without simultaneously damaging other biomolecules and cellular structures. Here we directly test whether highly toxic DNA double-strand breaks (DSBs) alone can drive an ageing phenotype using an adenovirus-based system based on tetracycline-controlled expression of the SacI restriction enzyme. We deliver the adenovirus to mice and compare molecular and cellular end points in the liver with normally aged animals. Treated, 3-month-old mice display many, but not all signs of normal liver ageing as early as 1 month after treatment, including ageing pathologies, markers of senescence, fused mitochondria and alterations in gene expression profiles. These results, showing that DSBs alone can cause distinct ageing phenotypes in mouse liver, provide new insights in the role of DNA damage as a driver of tissue ageing., Accumulation of DNA damage is a hallmark of cellular ageing but cause and effect are unclear. Here White et al. induce clean DNA double-strand breaks in the liver of mice using a modified restriction enzyme and demonstrate that DNA damage alone is sufficient to recapitulate some aspects of tissue ageing.

Published
2015

227. An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA

Author

Demaria, Marco, Ohtani, Naoko, Youssef Hassan, Sameh, Rodier, Francis, Toussaint, Wendy, Mitchell, James R, Laberge, Remi-Martin, Vijg, Jan, Van Steeg, Harry, Dollé, Martijn E T, Hoeijmakers, Jan H J, de Bruin, Alain, Hara, Eiji, Campisi, Judith, PB TR, Tissue Repair, LS Pathobiologie, Restoring Organ Function by Means of Regenerative Medicine (REGENERATE), PB TR, Tissue Repair, and LS Pathobiologie

Subjects
Male, Platelet-derived growth factor, Luminescence, Cellular differentiation, medicine.medical_treatment, Apoptosis, Mice, Transgenic, General Biochemistry, Genetics and Molecular Biology, Transgenic, Mesoderm, chemistry.chemical_compound, Mice, medicine, Animals, Transgenes, Senolytic, Myofibroblasts, Molecular Biology, Cellular Senescence, Platelet-Derived Growth Factor, Wound Healing, biology, Growth factor, fungi, Endothelial Cells, Cell Differentiation, Cell Biology, Fibroblasts, Cell biology, chemistry, Cell Aging, Immunology, biology.protein, Female, Wound healing, Myofibroblast, Cell aging, Platelet-derived growth factor receptor, Developmental Biology
Abstract

Cellular senescence suppresses cancer by halting the growth of premalignant cells, yet the accumulation of senescent cells is thought to drive age-related pathology through a senescence-associated secretory phenotype (SASP), the function of which is unclear. To understand the physiological role(s) of the complex senescent phenotype, we generated a mouse model in which senescent cells can be visualized and eliminated in living animals. We show that senescent fibroblasts and endothelial cells appear very early in response to a cutaneous wound, where they accelerate wound closure by inducing myofibroblast differentiation through the secretion of platelet-derived growth factor AA (PDGF-AA). In two mouse models, topical treatment of senescence-free wounds with recombinant PDGF-AA rescued the delayed wound closure and lack of myofibroblast differentiation. These findings define a beneficial role for the SASP in tissue repair and help to explain why the SASP evolved.

Published
2014

228. The double life of DNA

Author

McMurray, Cynthia T. and Vijg, Jan

Subjects
Aging, DNA Repair, Animals, Humans, Disease, DNA, Molecular Biology, Article, DNA Damage
Abstract

This issue of Current Opinions focuses on the dual role of DNA in life and death. In ancient Roman religion and myth, Janus is the god who looks both to the past and to the future. He guides the beginnings of life, its progression from one condition to another, and he foresees distant events. The analogy to DNA could not be stronger. Closely interacting with the environment, our basic genetics provides the origin of life, guides the quality of health with age, predicts disease, and ultimately foresees our end. A shared and deep interest in the origin of life has long prompted our desire to define aging, and, ultimately, to understand whether it can be reversed. In this special issue, the authors collectively review concepts of normative aging, DNA instability, DNA repair, the genetic contribution of age and diet to disease, and how the basic molecular transactions of DNA give it a double life that guides health and survival, as well as the transitions to death.

Published
2014

229. A review of the biomedical innovations for healthy longevity

Author

Moskalev, Alexey, primary, Anisimov, Vladimir, additional, Aliper, Aleksander, additional, Artemov, Artem, additional, Asadullah, Khusru, additional, Belsky, Daniel, additional, Baranova, Ancha, additional, de Grey, Aubrey, additional, Dixit, Vishwa Deep, additional, Debonneuil, Edouard, additional, Dobrovolskaya, Eugenia, additional, Fedichev, Peter, additional, Fedintsev, Alexander, additional, Fraifeld, Vadim, additional, Franceschi, Claudio, additional, Freer, Rosie, additional, Fülöp, Tamas, additional, Feige, Jerome, additional, Gems, David, additional, Gladyshev, Vadim, additional, Gorbunova, Vera, additional, Irincheeva, Irina, additional, Jager, Sibylle, additional, Jazwinski, S. Michal, additional, Kaeberlein, Matt, additional, Kennedy, Brian, additional, Khaltourina, Daria, additional, Kovalchuk, Igor, additional, Kovalchuk, Olga, additional, Kozin, Sergey, additional, Kulminski, Alexander, additional, Lashmanova, Ekaterina, additional, Lezhnina, Ksenia, additional, Liu, Guang-Hui, additional, Longo, Valter, additional, Mamoshina, Polina, additional, Maslov, Alexander, additional, Pedro de Magalhaes, Joao, additional, Mitchell, James, additional, Mitnitski, Arnold, additional, Nikolsky, Yuri, additional, Ozerov, Ivan, additional, Pasyukova, Elena, additional, Peregudova, Darya, additional, Popov, Vasily, additional, Proshkina, Ekaterina, additional, Putin, Evgeny, additional, Rogaev, Evgeny, additional, Rogina, Blanka, additional, Schastnaya, Jane, additional, Seluanov, Andrey, additional, Shaposhnikov, Mikhail, additional, Simm, Andreas, additional, Skulachev, Vladimir, additional, Skulachev, Maxim, additional, Solovev, Ilya, additional, Spindler, Stephen, additional, Stefanova, Natalia, additional, Suh, Yousin, additional, Swick, Andrew, additional, Tower, John, additional, Gudkov, Andrei V., additional, Vijg, Jan, additional, Voronkov, Andrey, additional, West, Michael, additional, Wagner, Wolfgang, additional, Yashin, Anatoliy, additional, Zemskaya, Nadezhda, additional, Zhumadilov, Zhaxybay, additional, and Zhavoronkov, Alex, additional

Published
2017
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233. Whole Chromosome Instability induces senescence and promotes SASP.

Author

Andriani, Grasiella Angelina, Andriani, Grasiella Angelina, Almeida, Vinnycius Pereira, Faggioli, Francesca, Mauro, Maurizio, Tsai, Wanxia Li, Santambrogio, Laura, Maslov, Alexander, Gadina, Massimo, Campisi, Judith, Vijg, Jan, Montagna, Cristina, Andriani, Grasiella Angelina, Andriani, Grasiella Angelina, Almeida, Vinnycius Pereira, Faggioli, Francesca, Mauro, Maurizio, Tsai, Wanxia Li, Santambrogio, Laura, Maslov, Alexander, Gadina, Massimo, Campisi, Judith, Vijg, Jan, and Montagna, Cristina

Abstract

Age-related accumulation of ploidy changes is associated with decreased expression of genes controlling chromosome segregation and cohesin functions. To determine the consequences of whole chromosome instability (W-CIN) we down-regulated the spindle assembly checkpoint component BUB1 and the mitotic cohesin SMC1A, and used four-color-interphase-FISH coupled with BrdU incorporation and analyses of senescence features to reveal the fate of W-CIN cells. We observed significant correlations between levels of not-diploid cells and senescence-associated features (SAFs). W-CIN induced DNA double strand breaks and elevated oxidative stress, but caused low apoptosis. SAFs of W-CIN cells were remarkably similar to those induced by replicative senescence but occurred in only 13 days versus 4 months. Cultures enriched with not-diploid cells acquired a senescence-associated secretory phenotype (SASP) characterized by IL1B, CXCL8, CCL2, TNF, CCL27 and other pro-inflammatory factors including a novel SASP component CLEC11A. These findings suggest that W-CIN triggers premature senescence, presumably to prevent the propagation of cells with an abnormal DNA content. Cells deviating from diploidy have the ability to communicate with their microenvironment by secretion of an array of signaling factors. Our results suggest that aneuploid cells that accumulate during aging in some mammalian tissues potentially contribute to age-related pathologies and inflammation through SASP secretion.

Published
2016

235. In silico Pathway Activation Network Decomposition Analysis (iPANDA) as a method for biomarker development

Author

Ozerov, Ivan V., primary, Lezhnina, Ksenia V., additional, Izumchenko, Evgeny, additional, Artemov, Artem V., additional, Medintsev, Sergey, additional, Vanhaelen, Quentin, additional, Aliper, Alexander, additional, Vijg, Jan, additional, Osipov, Andreyan N., additional, Labat, Ivan, additional, West, Michael D., additional, Buzdin, Anton, additional, Cantor, Charles R., additional, Nikolsky, Yuri, additional, Borisov, Nikolay, additional, Irincheeva, Irina, additional, Khokhlovich, Edward, additional, Sidransky, David, additional, Camargo, Miguel Luiz, additional, and Zhavoronkov, Alex, additional

Published
2016
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236. Whole Chromosome Instability induces senescence and promotes SASP

Author

Andriani, Grasiella Angelina, primary, Almeida, Vinnycius Pereira, additional, Faggioli, Francesca, additional, Mauro, Maurizio, additional, Tsai, Wanxia Li, additional, Santambrogio, Laura, additional, Maslov, Alexander, additional, Gadina, Massimo, additional, Campisi, Judith, additional, Vijg, Jan, additional, and Montagna, Cristina, additional

Published
2016
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242. Sensitivity of primary fibroblasts in culture to atmospheric oxygen does not correlate with species lifespan

Author

Patrick, Alison, primary, Seluanov, Michael, additional, Hwang, Chaewon, additional, Tam, Jonathan, additional, Khan, Tanya, additional, Morgenstern, Ari, additional, Wiener, Lauren, additional, Vazquez, Juan M., additional, Zafar, Hiba, additional, Wen, Robert, additional, Muratkalyeva, Malika, additional, Doerig, Katherine, additional, Zagorulya, Maria, additional, Cole, Lauren, additional, Catalano, Sophia, additional, Lobo Ladd, Aliny AB, additional, Coppi, A. Augusto, additional, Coşkun, Yüksel, additional, Tian, Xiao, additional, Ablaeva, Julia, additional, Nevo, Eviatar, additional, Gladyshev, Vadim N., additional, Zhang, Zhengdong D., additional, Vijg, Jan, additional, Seluanov, Andrei, additional, and Gorbunova, Vera, additional

Published
2016
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244. The progeroid phenotype of Ku80 deficiency is dominant over DNA-PKCS deficiency

Author

Reiling, Erwin, Dollé, Martijn E T, Youssef, Sameh A, Lee, Moonsook, Nagarajah, Bhawani, Roodbergen, Marianne, de With, Piet, de Bruin, Alain, Hoeijmakers, Jan H, Vijg, Jan, van Steeg, Harry, Hasty, Paul, LS Pathobiologie, PB TR, Tissue Repair, Molecular Genetics, Surgery, LS Pathobiologie, PB TR, and Tissue Repair

Subjects
Male, Aging, Ku80, DNA End-Joining Repair, Mutant, lcsh:Medicine, DNA-Activated Protein Kinase, medicine.disease_cause, Inbred C57BL, Gene Knockout Techniques, Mice, 0302 clinical medicine, Mutation frequency, lcsh:Science, DNA-PKcs, 0303 health sciences, Ku70, Mutation, Multidisciplinary, Nuclear Proteins, Antigens, Nuclear, Non-homologous end joining, DNA-Binding Proteins, Phenotype, 030220 oncology & carcinogenesis, Female, biological phenomena, cell phenomena, and immunity, Research Article, DNA damage, Longevity, Biology, 03 medical and health sciences, Genetics, Cancer Genetics, medicine, Animals, Nuclear, Antigens, Ku Autoantigen, 030304 developmental biology, lcsh:R, Body Weight, Biology and Life Sciences, Molecular biology, Mice, Inbred C57BL, enzymes and coenzymes (carbohydrates), Immunology, lcsh:Q, Animal Genetics, DNA Damage
Abstract

Ku80 and DNA-PKCS are both involved in the repair of double strand DNA breaks via the nonhomologous end joining (NHEJ) pathway. While ku80(-/-) mice exhibit a severely reduced lifespan and size, this phenotype is less pronounced in dna-pk(cs)(-/-) mice. However, these observations are based on independent studies with varying genetic backgrounds. Here, we generated ku80(-/-), dna-pk(cs)(-/-) and double knock out mice in a C57Bl6/J*FVB F1 hybrid background and compared their lifespan, end of life pathology and mutation frequency in liver and spleen using a lacZ reporter. Our data confirm that inactivation of Ku80 and DNA-PKCS causes reduced lifespan and bodyweights, which is most severe in ku80(-/-) mice. All mutant mice exhibited a strong increase in lymphoma incidence as well as other aging-related pathology (skin epidermal and adnexal atrophy, trabacular bone reduction, kidney tubular anisokaryosis, and cortical and medullar atrophy) and severe lymphoid depletion. LacZ mutation frequency analysis did not show strong differences in mutation frequencies between knock out and wild type mice. The ku80(-/-) mice had the most severe phenotype and the Ku80-mutation was dominant over the DNA-PKCS-mutation. Presumably, the more severe degenerative effect of Ku80 inactivation on lifespan compared to DNA-PKCS inactivation is caused by additional functions of Ku80 or activity of free Ku70 since both Ku80 and DNA-PKCS are essential for NHEJ.

Published
2014
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246. Cell Replacement to Reverse Brain Aging: Challenges, Pitfalls, and Opportunities.

Author

Hébert, Jean M. and Vijg, Jan

Subjects
*AGING prevention, *NEURAL stem cells, *AGING, *BRAIN, *NEOCORTEX, *NEURONS
Abstract

Current antiaging strategies focusing on druggable targets have met with relatively limited success to date. Replacement of cells, tissues, and organs could provide an alternative means for targeting age-induced damage and potentially eliminating some of it. However, before this is a viable option, numerous challenges need to be addressed. Most notably, whether the brain, which defines our self-identity, is amenable to replacement therapies is unclear. Here, we consider whether progressive cell replacement is a potential approach to reverse brain aging without grossly altering function. We focus mainly on the neocortex, seat of our highest cognitive functions, because of abundant knowledge on neocortical development, plasticity, and how the neocortex can functionally incorporate new neurons. We outline the primary challenges for brain cell replacement, and key areas that require further investigation. [ABSTRACT FROM AUTHOR]

Published
2018
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247. The American Technological Challenge

Author

Vijg, Jan and Vijg, Jan

Subjects
Technology--History--21st century, Technology and civilization
Abstract

The American Technological Challenge - Stagnation and Decline in the 21st Century refutes the myth that we live in the most innovative of times. Inventions themselves are only one of the factors that determine the technological fate of a society. Sometimes, inventions are adopted, and eagerly; sometimes not. The history of technological progress, and the historical and societal factors that impel or restrain the adoption of inventions, are explored in the book.New, life-changing inventions have become rare and in spite of ample vocal support of innovation, an increasingly complacent society has lost its taste for risk and often actively resists change. Far from being unique, technology slowdowns are recurrent events in history, occurring in civilizations that have reached the zenith of their success. They are the inevitable fate of an increasingly regulated, successful society. Most people would characterize the dawn of the 21st century as the age of technological progress par excellence. If you are one of them, then, think again. While our parents, grandparents and great-grandparents witnessed life-changing inventions every decade, very little major new technology has seen the light of day over the last half century. We find ourselves in the midst of a technology slowdown!This book is about the causes and consequences of technology slowdowns, which are not unique but recurrent events in human history. They occur not in times of upheaval, when violent interstate conflicts are the order of the day. Such periods foster innovation and allow major, breakthrough inventions to be adopted quickly. Instead, innovation seriously stalls in times that are peaceful, when governments reign supreme and citizens are encapsulated by layers of benign regulation to protect them against all possible harm. We find ourselves in the best of times. The long period of bloody combat that characterized so much of the 20th century has finally ended. Violent conflicts between states are minimal and conditions for almost everyone on the planet are on an upswing, with poverty on the decline and life expectancy and literacy increasing. Responsible government and industry leaders have begun to refrain from risky bets on exciting new exploits and the time of grand projects, such as the Eisenhower Interstate System, the Moon Landing Program or the development of the internet is behind us. Instead, we have to make do with incremental improvements of existing technology, catch-up programs in developing countries and social programs. The consequences are stalling wealth generation and an end to the dramatic changes society has undergone since the industrial revolution now more than 200 years ago.

Published
2011

248. A mechanism for inheriting radiation-induced DNA damage.

Author

Cutler, Ronald and Vijg, Jan

Abstract

Radiation-damaged paternal DNA has been found to cause embryos of the second generation of nematode worms, but not the first, to die. The proposed mechanisms help to explain the observed lack of such an effect in humans.Transgenerational inheritance of DNA damage by error-prone DNA repair. [ABSTRACT FROM AUTHOR]

Published
2023
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249. Measuring cell-to-cell expression variability in single-cell RNA-sequencing data: a comparative analysis and applications to B cell aging

Author

Zheng, Huiwen, Vijg, Jan, Fard, Atefeh Taherian, and Mar, Jessica Cara

Abstract

Background: Single-cell RNA-sequencing (scRNA-seq) technologies enable the capture of gene expression heterogeneity and consequently facilitate the study of cell-to-cell variability at the cell type level. Although different methods have been proposed to quantify cell-to-cell variability, it is unclear what the optimal statistical approach is, especially in light of challenging data structures that are unique to scRNA-seq data like zero inflation. Results: We systematically evaluate the performance of 14 different variability metrics that are commonly applied to transcriptomic data for measuring cell-to-cell variability. Leveraging simulations and real datasets, we benchmark the metric performance based on data-specific features, sparsity and sequencing platform, biological properties, and the ability to recapitulate true levels of biological variability based on known gene sets. Next, we use scran, the metric with the strongest all-round performance, to investigate changes in cell-to-cell variability that occur during B cell differentiation and the aging processes. The analysis of primary cell types from hematopoietic stem cells (HSCs) and B lymphopoiesis reveals unique gene signatures with consistent patterns of variable and stable expression profiles during B cell differentiation which highlights the significance of these methods. Identifying differentially variable genes between young and old cells elucidates the regulatory changes that may be overlooked by solely focusing on mean expression changes and we investigate this in the context of regulatory networks. Conclusions: We highlight the importance of capturing cell-to-cell gene expression variability in a complex biological process like differentiation and aging and emphasize the value of these findings at the level of individual cell types.

Published
2023
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250. Genetic wrinkles in time

Author

Cutler, Ronald and Vijg, Jan

Abstract

Cutler and Vijg remind us of the publication that laid the foundation for genetic mutation theories of ageing.

Published
2023
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