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cell clonality and senescence

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https://www.readbyqxmd.com/read/28588756/immunological-aspects-of-age-related-diseases
#1
REVIEW
Ken-Ichi Isobe, Naomi Nishio, Tadao Hasegawa
The proportion of elderly people rises in the developed countries. The increased susceptibility of the elderly to infectious diseases is caused by immune dysfunction, especially T cell functional decline. Age-related hematopoietic stem cells deviate from lymphoid lineage to myeloid lineage. Thymus shrinks early in life, which is followed by the decline of naïve T cells. T-cell receptor repertoire diversity declines by aging, which is caused by cytomegalovirus-driven T cell clonal expansion. Functional decline of B cell induces antibody affinity declines by aging...
May 26, 2017: World Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28341737/an-abnormal-bone-marrow-microenvironment-contributes-to-hematopoietic-dysfunction-in-fanconi-anemia
#2
Yuan Zhou, Yongzheng He, Wen Xing, Peng Zhang, Hui Shi, Shi Chen, Jun Shi, Jie Bai, Steven D Rhodes, Fengqui Zhang, Jin Yuan, Xianlin Yang, Xiaofan Zhu, Yan Li, Helmut Hanenberg, Mingjiang Xu, Kent A Robertson, Weiping Yuan, Grzegorz Nalepa, Tao Cheng, D Wade Clapp, Feng-Chun Yang
Fanconi anemia is a complex heterogeneous genetic disorder with a high incidence of bone marrow failure, clonal evolution to acute myeloid leukemia and mesenchymal-derived congenital anomalies. Increasing evidence in Fanconi anemia and other genetic disorders points towards an interdependence of skeletal and hematopoietic development, yet the impact of the marrow microenvironment in the pathogenesis of the bone marrow failure in Fanconi anemia remains unclear. Here we demonstrated that mice with double knockout of both Fancc and Fancg genes had decreased bone formation at least partially due to impaired osteoblast differentiation from mesenchymal stem/progenitor cells...
June 2017: Haematologica
https://www.readbyqxmd.com/read/28167050/changing-mutational-and-adaptive-landscapes-and-the-genesis-of-cancer
#3
L Alexander Liggett, James DeGregori
By the time the process of oncogenesis has produced an advanced cancer, tumor cells have undergone extensive evolution. The cellular phenotypes resulting from this evolution have been well studied, and include accelerated growth rates, apoptosis resistance, immortality, invasiveness, and immune evasion. Yet with all of our current knowledge of tumor biology, the details of early oncogenesis have been difficult to observe and understand. Where different oncogenic mutations may work together to enhance the survival of a tumor cell, in isolation they are often pro-apoptotic, pro-differentiative or pro-senescent, and therefore often, somewhat paradoxically, disadvantageous to a cell...
February 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28150695/characterisation-of-a-divergent-progenitor-cell-sub-populations-in-human-osteoarthritic-cartilage-the-role-of-telomere-erosion-and-replicative-senescence
#4
Christopher R Fellows, Rebecca Williams, Iwan R Davies, Kajal Gohil, Duncan M Baird, John Fairclough, Paul Rooney, Charles W Archer, Ilyas M Khan
In recent years it has become increasingly clear that articular cartilage harbours a viable pool of progenitor cells and interest has focussed on their role during development and disease. Analysis of progenitor numbers using fluorescence-activated sorting techniques has resulted in wide-ranging estimates, which may be the result of context-dependent expression of cell surface markers. We have used a colony-forming assay to reliably determine chondroprogenitor numbers in normal and osteoarthritic cartilage where we observed a 2-fold increase in diseased tissue (P  < 0...
February 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28148303/variation-in-human-dental-pulp-stem-cell-ageing-profiles-reflect-contrasting-proliferative-and-regenerative-capabilities
#5
Amr Alraies, Nadia Y A Alaidaroos, Rachel J Waddington, Ryan Moseley, Alastair J Sloan
BACKGROUND: Dental pulp stem cells (DPSCs) are increasingly being recognized as a viable cell source for regenerative medicine. Although significant variations in their ex vivo expansion are well-established, DPSC proliferative heterogeneity remains poorly understood, despite such characteristics influencing their regenerative and therapeutic potential. This study assessed clonal human DPSC regenerative potential and the impact of cellular senescence on these responses, to better understand DPSC functional behaviour...
February 2, 2017: BMC Cell Biology
https://www.readbyqxmd.com/read/28121388/early-life-infection-but-not-breastfeeding-predicts-adult-blood-telomere-lengths-in-the-philippines
#6
Dan T A Eisenberg, Judith B Borja, M Geoffrey Hayes, Christopher W Kuzawa
OBJECTIVES: Telomeres are repetitive DNA at chromosomes ends that shorten with age due to cellular replication and oxidative stress. As telomeres shorten, this can eventually place limits on cell replication and contribute to senescence. Infections are common during early development and activate cellular immune responses that involve clonal expansion and oxidative stress. As such, a high infectious disease burden might shorten blood telomere length (BTL) and accelerate the pace of immune senescence...
January 25, 2017: American Journal of Human Biology: the Official Journal of the Human Biology Council
https://www.readbyqxmd.com/read/28117106/stress-induced-premature-senescence-of-dermal-papilla-cells-compromises-hair-follicle-epithelial-mesenchymal-interaction
#7
Wen-Yen Huang, Yi-Ching Huang, Kai-Shin Huang, Chih-Chieh Chan, Hsien-Yi Chiu, Ren-Yeu Tsai, Jung-Yi Chan, Sung-Jan Lin
BACKGROUND: Hair follicle is miniorgan constituted by keratinocytes and its distinctive mesenchyme of dermal papilla. Its aging is characterized by organ atrophy and impaired stem cell activation and differentiation. The contribution of dermal papilla to hair follicle aging change is not well understood. OBJECTIVE: This work was aimed at exploring the possible role of premature dermal papilla senescence in the pathogenesis of hair follicle aging. METHODS: Dermal papilla cells were challenged with H2O2 to induce premature senescence and the proliferation, apoptosis, gene expression and protein secretion were characterized...
May 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28076901/nuclear-factor-one-transcription-factors-as-epigenetic-regulators-in-cancer
#8
REVIEW
Mitchell Fane, Lachlan Harris, Aaron G Smith, Michael Piper
Tumour heterogeneity poses a distinct obstacle to therapeutic intervention. While the initiation of tumours across various physiological systems is frequently associated with signature mutations in genes that drive proliferation and bypass senescence, increasing evidence suggests that tumour progression and clonal diversity is driven at an epigenetic level. The tumour microenvironment plays a key role in driving diversity as cells adapt to demands imposed during tumour growth, and is thought to drive certain subpopulations back to a stem cell-like state...
January 11, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27785870/senescence-associated-dna-methylation-is-stochastically-acquired-in-subpopulations-of-mesenchymal-stem-cells
#9
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...
February 2017: Aging Cell
https://www.readbyqxmd.com/read/27769870/braf-exon-15-mutations-in-pediatric-renal-stromal-tumors-prevalence-in-metanephric-stromal-tumors
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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