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cell clonality and senescence

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https://www.readbyqxmd.com/read/27785870/senescence-associated-dna-methylation-is-stochastically-acquired-in-subpopulations-of-mesenchymal-stem-cells
#1
Julia Franzen, Anne Zirkel, Jonathon Blake, Björn Rath, Vladimir Benes, Argyris Papantonis, Wolfgang Wagner
Replicative senescence has a major impact on function and integrity of cell preparations. This process is reflected by continuous DNA methylation (DNAm) changes at specific CpG dinucleotides in the course of in vitro culture, and such modifications can be used to estimate the state of cellular senescence for quality control of cell preparations. Still, it is unclear how senescence-associated DNAm changes are regulated and whether they occur simultaneously across a cell population. In this study, we analyzed global DNAm profiles of human mesenchymal stem cells (MSCs) and human umbilical vein endothelial cells (HUVECs) to demonstrate that senescence-associated DNAm changes are overall similar in these different cell types...
October 26, 2016: Aging Cell
https://www.readbyqxmd.com/read/27769870/braf-exon-15-mutations-in-pediatric-renal-stromal-tumors-prevalence-in-metanephric-stromal-tumors
#2
Lily Marsden, Lawrence J Jennings, Samantha Gadd, Min Yu, Elizabeth J Perlman, Mariana M Cajaiba
Metanephric stromal tumors are rare renal stromal tumors that predominantly affect children. They belong to the metanephric family of tumors along with metanephric adenofibroma and metanephric adenoma. The previous documentation of BRAF exon 15 mutations in 88% of metanephric adenomas and in isolated cases of metanephric adenofibroma prompted us to investigate the prevalence of these mutations in metanephric stromal tumors and in other pediatric renal stromal tumors. In this study, 17 metanephric stromal tumors, 22 congenital mesoblastic nephromas and 6 ossifying renal tumors of infancy were selected for BRAF exon 15 testing...
October 18, 2016: Human Pathology
https://www.readbyqxmd.com/read/27754273/sy-17-3-role-of-cmv-induced-t-cell-senescence-in-the-pathophysiology-of-cardiovascular-disease
#3
Jong-Chan Youn
Immunosenescence, defined as the age-associated dysregulation and dysfunction of the immune system, is characterized by impaired protective immunity and decreased efficacy of vaccines. Immunosenescence affects both the innate and adaptive immune systems; however, the most notable changes are in T cell immunity and include thymic involution, the collapse of T cell receptor (TCR) diversity, an imbalance in T cell populations, and the clonal expansion of senescent T cells. An increasing number of immunological, clinical and epidemiological studies suggest that persistent Cytomegalovirus (CMV) infection is associated with accelerated aging of the immune system and T cell immunosenescence especially...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27643270/sy-17-3-role-of-cmv-induced-t-cell-senescence-in-the-pathophysiology-of-cardiovascular-disease
#4
Jong-Chan Youn
Immunosenescence, defined as the age-associated dysregulation and dysfunction of the immune system, is characterized by impaired protective immunity and decreased efficacy of vaccines. Immunosenescence affects both the innate and adaptive immune systems; however, the most notable changes are in T cell immunity and include thymic involution, the collapse of T cell receptor (TCR) diversity, an imbalance in T cell populations, and the clonal expansion of senescent T cells. An increasing number of immunological, clinical and epidemiological studies suggest that persistent Cytomegalovirus (CMV) infection is associated with accelerated aging of the immune system and T cell immunosenescence especially...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27631279/cohesion-of-clonal-life-history-senescence-and-rejuvenation-induced-by-autogamy-of-the-histophagous-ciliate-tetrahymena-rostrata
#5
Andrzej Kaczanowski, Clifford F Brunk, Stanislaw L Kazubski
The histophagous ciliate Tetrahymena rostrata was found as a parasite in the renal organs of the land snails Zonitoides nitidus and Cochlicopa lubrica. A starvation medium induced encystment, meiosis, autogamy, and development of new macronuclei. The cell division rate declined linearly with number of divisions from the last autogamy until senescence. The senescing strains were rejuvenated by further encystment-induced autogamy. It is expected, that these processes contribute to genetic variability among the local, small, and isolated T...
November 2016: Protist
https://www.readbyqxmd.com/read/27380967/aging-clonality-and-rejuvenation-of-hematopoietic-stem-cells
#6
REVIEW
Shailaja Akunuru, Hartmut Geiger
Aging is associated with reduced organ function and increased disease incidence. Hematopoietic stem cell (HSC) aging driven by both cell intrinsic and extrinsic factors is linked to impaired HSC self-renewal and regeneration, aging-associated immune remodeling, and increased leukemia incidence. Compromised DNA damage responses and the increased production of reactive oxygen species (ROS) have been previously causatively attributed to HSC aging. However, recent paradigm-shifting concepts, such as global epigenetic and cytoskeletal polarity shifts, cellular senescence, as well as the clonal selection of HSCs upon aging, provide new insights into HSC aging mechanisms...
August 2016: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/27183600/the-hayflick-limit-may-determine-the-effective-clonal-diversity-of-naive-t-cells
#7
Wilfred Ndifon, Jonathan Dushoff
Having a large number of sufficiently abundant T cell clones is important for adequate protection against diseases. However, as shown in this paper and elsewhere, between young adulthood and >70 y of age the effective clonal diversity of naive CD4/CD8 T cells found in human blood declines by a factor of >10. (Effective clonal diversity accounts for both the number and the abundance of T cell clones.) The causes of this observation are incompletely understood. A previous study proposed that it might result from the emergence of certain rare, replication-enhancing mutations in T cells...
June 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27169376/a-mechanistic-evaluation-of-the-syrian-hamster-embryo-cell-transformation-assay-ph-6-7-and-molecular-events-leading-to-senescence-bypass-in-she-cells
#8
Jessica C Pickles, Kamala Pant, Lisa A Mcginty, Hemad Yasaei, Terry Roberts, Andrew D Scott, Robert F Newbold
The implementation of the Syrian hamster embryo cell transformation assay (SHE CTA) into test batteries and its relevance in predicting carcinogenicity has been long debated. Despite prevalidation studies to ensure reproducibility and minimise the subjective nature of the assay's endpoint, an underlying mechanistic and molecular basis supporting morphological transformation (MT) as an indicator of carcinogenesis is still missing. We found that only 20% of benzo(a)pyrene-induced MT clones immortalised suggesting that, alone, the MT phenotype is insufficient for senescence bypass...
May 2016: Mutation Research. Genetic Toxicology and Environmental Mutagenesis
https://www.readbyqxmd.com/read/27158641/microwell-arrays-reveal-cellular-heterogeneity-during-the-clonal-expansion-of-transformed-human-cells
#9
Tim C Chang, Weiliang Tang, William Jen Hoe Koh, Alexander J E Rettie, Mary J Emond, Raymond J Monnat, Albert Folch
We developed micromolded microwell arrays to study the proliferation and senescence of single cells. Microwell arrays were designed to be compatible with conventional cell culture protocols to simplify cell loading, cell culture, and imaging. We demonstrated the utility of these arrays by measuring the proliferation and senescence of isogenic cells which expressed or had been depleted of the human Werner syndrome protein. Our results allowed us to reveal cell-to-cell heterogeneity in proliferation in WRN+ and WRN-depleted fibroblasts during clonal growth...
December 2015: Technology
https://www.readbyqxmd.com/read/27146030/endometrial-mesenchymal-stem-stromal-cells-their-fibroblast-progeny-in-endometriosis-and-more
#10
Caroline E Gargett, Shanti Gurung
No abstract text is available yet for this article.
June 2016: Biology of Reproduction
https://www.readbyqxmd.com/read/27102208/multiple-myeloma-causes-clonal-t-cell-immunosenescence-identification-of-potential-novel-targets-for-promoting-tumour-immunity-and-implications-for-checkpoint-blockade
#11
H Suen, R Brown, S Yang, C Weatherburn, P J Ho, N Woodland, N Nassif, P Barbaro, C Bryant, D Hart, J Gibson, D Joshua
Tumour-induced dysfunction of cytotoxic T cells in patients with multiple myeloma (MM) may contribute to immune escape and be responsible for the lack of therapeutic efficacy of immune checkpoint blockade. We therefore investigated dysfunctional clonal T cells in MM and demonstrated immunosenescence but not exhaustion as a predominant feature. T-cell clones were detected in 75% of MM patients and their prognostic significance was revalidated in a new post-immunomodulatory drug cohort. The cells exhibited a senescent secretory effector phenotype: KLRG-1+/CD57+/CD160+/CD28-...
August 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/26984302/metal-mixture-as-cd-pb-induced-cell-transformation-is-modulated-by-ola1
#12
Elia Martínez-Baeza, Emilio Rojas, Mahara Valverde
Environmental pollutants are complex mixtures in which metals are ubiquitous. Metal mixtures of arsenic, cadmium and lead are present in the occupational environment and generate health effects such as cardiovascular, renal and cancer diseases. Cell transformation induced by metal mixtures that depend on reactive oxygen species (ROS) generation, cell viability maintenance and avoidance of senescence was previously reported by our group. The aim of the present study was to explore the role of a Obg-like ATPase1 (OLA1) in the cell transformation of BALB/c 3T3 A31-1-1 clonal cells induced by a metal mixture (2 µM NaAsO2, 2 µM CdCl2 and 5 µM Pb(C2H3O2)2 3H2O) through ROS generation...
July 2016: Mutagenesis
https://www.readbyqxmd.com/read/26647820/quantifying-replicative-senescence-as-a-tumor-suppressor-pathway-and-a-target-for-cancer-therapy
#13
Ignacio A Rodriguez-Brenes, Dominik Wodarz, Natalia L Komarova
To study quantitatively replicative senescence as a tumor suppressor mechanism, we investigate the distribution of a growing clonal cell population restricted by Hayflick's limit. We find that in the biologically relevant range of parameters, if the imbalance between cell division and death is moderate or low (high death-to-birth ratio), senescence offers significant protection against cancer by halting abnormal cell proliferation at early pre-diagnostic stages of tumor development. We also find that by the time tumors are typically detected, there is a high probability that telomerase is activated, even if the cell of origin was telomerase negative...
2015: Scientific Reports
https://www.readbyqxmd.com/read/26528855/efficacy-of-cdk4-inhibition-against-sarcomas-depends-on-their-levels-of-cdk4-and-p16ink4-mrna
#14
Marco Perez, Sandra Muñoz-Galván, Manuel P Jiménez-García, Juan J Marín, Amancio Carnero
Sarcomas are malignant tumors accounting for a high percentage of cancer morbidity and mortality in children and young adults. Surgery and radiation therapy are the accepted treatments for most sarcomas; however, patients with metastatic disease are treated with systemic chemotherapy. Many tumors display marginal levels of chemoresponsiveness and new treatment approaches are needed. Deregulation of the G1 checkpoint is crucial for various oncogenic transformation processes, suggesting that many cancer cell types depend on CDK4/6 activity...
December 1, 2015: Oncotarget
https://www.readbyqxmd.com/read/26469953/rac3-more-than-a-nuclear-receptor-coactivator-a-key-inhibitor-of-senescence-that-is-downregulated-in-aging
#15
P N Fernández Larrosa, M Ruíz Grecco, D Mengual Gómez, C V Alvarado, L C Panelo, M F Rubio, D F Alonso, D E Gómez, M A Costas
Receptor-associated coactivator 3 (RAC3) is a nuclear receptor coactivator usually overexpressed in tumors that exerts oncogenic functions in the cytoplasm and the nucleus. Although as part of its oncogenic actions it was previously identified as an inhibitor of apoptosis and autophagy, its expression is required in order to preserve the pluripotency and embryonic stem cell self-renewal. In this work we investigated its role in cellular senescence. We found that RAC3 overexpression in the nontumoral HEK293 cells inhibits the premature senescence induced by hydrogen peroxide or rapamycin...
2015: Cell Death & Disease
https://www.readbyqxmd.com/read/26300491/genetics-of-melanocytic-nevi
#16
REVIEW
Mi Ryung Roh, Philip Eliades, Sameer Gupta, Hensin Tsao
Melanocytic nevi are a benign clonal proliferation of cells expressing the melanocytic phenotype, with heterogeneous clinical and molecular characteristics. In this review, we discuss the genetics of nevi by salient nevi subtypes: congenital melanocytic nevi, acquired melanocytic nevi, blue nevi, and Spitz nevi. While the molecular etiology of nevi has been less thoroughly studied than melanoma, it is clear that nevi and melanoma share common driver mutations. Acquired melanocytic nevi harbor oncogenic mutations in BRAF, which is the predominant oncogene associated with melanoma...
November 2015: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/26274841/density-dependent-metabolic-heterogeneity-in-human-mesenchymal-stem-cells
#17
Yijun Liu, Nathalie Muñoz, Bruce A Bunnell, Timothy M Logan, Teng Ma
Human mesenchymal stem cells (hMSCs) are intrinsically heterogeneous and comprise subpopulations that differ in their proliferation, multi-potency, and functional properties, which are commonly demonstrated by culturing hMSCs at different plating densities. The objective of this study was to investigate the metabolic profiles of different subpopulations of hMSC by testing the hypothesis that the clonogenic hMSC subpopulation, which is selectively enriched in clonal density (CD) and low density (LD) culture (10 and 100 cells per square centimeter, respectively), possesses a metabolic phenotype that differs from that of hMSC in medium- or high-density (MD: 1,000 and HD: 3,000 cells per square centimeter, respectively)...
November 2015: Stem Cells
https://www.readbyqxmd.com/read/26195751/preventing-clonal-evolutionary-processes-in-cancer-insights-from-mathematical-models
#18
Ignacio A Rodriguez-Brenes, Dominik Wodarz
Clonal evolutionary processes can drive pathogenesis in human diseases, with cancer being a prominent example. To prevent or treat cancer, mechanisms that can potentially interfere with clonal evolutionary processes need to be understood better. Mathematical modeling is an important research tool that plays an ever-increasing role in cancer research. This paper discusses how mathematical models can be useful to gain insights into mechanisms that can prevent disease initiation, help analyze treatment responses, and aid in the design of treatment strategies to combat the emergence of drug-resistant cells...
July 21, 2015: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/26188489/t-cell-senescence-and-cardiovascular-diseases
#19
REVIEW
Hee Tae Yu, Sungha Park, Eui-Cheol Shin, Won-Woo Lee
Age-related changes in the immune system, commonly termed "immunosenescence," contribute to deterioration of the immune response and fundamentally impact the health and survival of elderly individuals. Immunosenescence affects both the innate and adaptive immune systems; however, the most notable changes are in T cell immunity and include thymic involution, the collapse of T cell receptor (TCR) diversity, an imbalance in T cell populations, and the clonal expansion of senescent T cells. Senescent T cells have the ability to produce large quantities of proinflammatory cytokines and cytotoxic mediators; thus, they have been implicated in the pathogenesis of many chronic inflammatory diseases...
August 2016: Clinical and Experimental Medicine
https://www.readbyqxmd.com/read/26136618/botryllus-schlosseri-an-emerging-model-for-the-study-of-aging-stem-cells-and-mechanisms-of-regeneration
#20
Ayelet Voskoboynik, Irving L Weissman
The decline of tissue regenerative potential with the loss of stem cell function is a hallmark of mammalian aging. We study Botryllus schlosseri, a colonial chordate which exhibits robust stem cell-mediated regeneration capacities throughout life. Larvae, derived by sexual reproduction and chordate development, metamorphose to clonal founders that undergo weekly formation of new individuals by budding from stem cells. Individuals are transient structures which die through massive apoptosis, and successive buds mature to replicate an entire new body...
January 30, 2015: Invertebrate Reproduction & Development
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