Sponges (Porifera) model systems to study the shift from immortal to senescent somatic cells: the telomerase activity in somatic cells

1998 ◽  
Vol 100 (2) ◽  
pp. 107-120 ◽  
Author(s):  
Claudia Koziol ◽  
Radovan Borojevic ◽  
Renate Steffen ◽  
Werner E.G Müller
Keyword(s):  
Somatic Cells ◽  
Telomerase Activity ◽  
Model Systems

scholarly journals Telomerase as a possible key to bypass the cost of reproduction effect

2022 ◽  
Author(s):  
Radmila Capkova Frydrychova
Keyword(s):  
Somatic Cells ◽  
Metabolic Stress ◽  
Cost Of Reproduction ◽  
Telomerase Activity ◽  
Model Systems ◽  
Aging Research ◽  
Eusocial Insects ◽  
Reproduction Strategy ◽  
Key Factor ◽  
Human Adults

Telomerase activity and telomere restoration in certain somatic cells of human adults maintain the proliferative capacity of these cells and contribute to their regenerative potential, and telomerase activity and telomere length are commonly considered lifespan predictors. Eusocial insects provide excellent model systems for aging research based on their extraordinary caste-related lifespan differences that contradict the typical fecundity/lifespan trade-off. In agreement with the common presumption, telomerase activity is upregulated in the reproductive, long-lived individuals of eusocial insects such as queens and kings, proposing that telomerase activity acts as a key factor in their extended longevity. But, as documented by the presence of telomerase in somatic tissues of numerous invertebrate and vertebrate species, the connection between telomerase activity and the predicted lifespan is not clear. Here, I ask whether somatic telomerase activity in eusocial reproductives may serve its non-canonical function to protect its individuals against the exacerbated metabolic stress upon reproduction and be a reflection of a more common phenomenon among species. I propose a hypothesis that the presence of telomerase activity in somatic cells reflects a different reproduction strategy of the species.

scholarly journals Generation of a Panel of Induced Pluripotent Stem Cells From Chimpanzees: a Resource for Comparative Functional Genomics

2014 ◽  
Author(s):  
Irene Gallego Romero ◽  
Bryan J Pavlovic ◽  
Irene Hernando-Herraez ◽  
Nicholas E Banovich ◽  
Courtney L Kagan ◽  
...  
Keyword(s):  
Somatic Cells ◽  
Induced Pluripotent Stem Cell ◽  
Cell Types ◽  
Model Systems ◽  
Sequencing Data ◽  
Differentiation Potential ◽  
Culture Techniques ◽  
Human Ipscs ◽  
Wide Range ◽  
Induced Pluripotent

Comparative genomics studies in primates are extremely restricted because we only have access to a few types of cell lines from non-human apes and to a limited collection of frozen tissues. In order to gain better insight into regulatory processes that underlie variation in complex phenotypes, we must have access to faithful model systems for a wide range of tissues and cell types. To facilitate this, we have generated a panel of 7 fully characterized chimpanzee (Pan troglodytes) induced pluripotent stem cell (iPSC) lines derived from fibroblasts of healthy donors. All lines appear to be free of integration from exogenous reprogramming vectors, can be maintained using standard iPSC culture techniques, and have proliferative and differentiation potential similar to human and mouse lines. To begin demonstrating the utility of comparative iPSC panels, we collected RNA sequencing data and methylation profiles from the chimpanzee iPSCs and their corresponding fibroblast precursors, as well as from 7 human iPSCs and their precursors, which were of multiple cell type and population origins. Overall, we observed much less regulatory variation within species in the iPSCs than in the somatic precursors, indicating that the reprogramming process has erased many of the differences observed between somatic cells of different origins. We identified 4,918 differentially expressed genes and 3,598 differentially methylated regions between iPSCs of the two species, many of which are novel inter-species differences that were not observed between the somatic cells of the two species. Our panel will help realise the potential of iPSCs in primate studies, and in combination with genomic technologies, transform studies of comparative evolution.

42 DEVELOPMENTAL POTENTIAL AND REPROGRAMMING EFFICIENCY OF BOVINE EMBRYOS CLONED WITH ADULT FIBROBLASTS TREATED BY A DEMETHYLATING AGENT, S-ADENOSYL-HOMOCYSTEINE

2006 ◽  
Vol 18 (2) ◽  
pp. 130 ◽  
Author(s):  
B.-G. Jeon ◽  
S. D. Perrault ◽  
G.-J. Rho ◽  
D. H. Betts ◽  
W. A. King
Keyword(s):  
Dna Methylation ◽  
Nuclear Transfer ◽  
Methylation Status ◽  
Somatic Cells ◽  
Telomerase Activity ◽  
Dna Demethylation ◽  
Blastocyst Development ◽  
Developmental Potential ◽  
Reprogramming Efficiency ◽  
Low Efficiency

Animal cloning by somatic cell nuclear transfer (SCNT) has been successfully applied to several species although with low efficiency and often associated with severe abnormalities. These poor outcomes are thought to be a consequence of aberrant DNA methylation patterns that result from incomplete epigenetic reprogramming of the transplanted nucleus into recipient oocytes. Telomerase, an enzyme not expressed in most somatic cells, should be expressed in cloned embryos. Therefore its activity has been used as an index of reprogramming in SCNT embryos. The objective of this study was to investigate the DNA methylation status of donor fibroblasts treated with a non-cytotoxic transmethylation inhibitor, S-adenosyl homocysteine (SAH), and to assess the relative telomerase activity (RTA) and developmental potential of SCNT embryos derived from such cells. Adult ear skin fibroblasts were cultured in DMEM supplemented with 0, 0.5, 1.0, or 2.0 mM SAH for 144 h by daily media change prior to nuclear transfer. The SAH-treated fibroblasts were immunostained with a fluorescein isothiocyanate (FITC) conjugated 5-methylcytosine antibody and the relative fluorescence intensity (RFI) was analyzed using a fluorescence microscope equipped with an Openlab" program (Improvision, Coventry, UK). RTA was measured in Day 8 SCNT blastocysts using the real-time quantitative telomeric repeat amplification protocol (RQ-TRAP). Fibroblasts treated with 0.5, 1.0, and 2.0 mM SAH showed lower levels of DNA methylation compared to nontreated controls, and the values did not differ among the treatment groups. Cleavage rates did not differ between the SCNT embryos derived from 0.5 mM SAH-treated cells and nontreated control cells (92.3% vs. 91.3%, respectively). However, the rates of blastocyst development and hatching were significantly (P < 0.05) higher in SCNT embryos derived from 0.5 mM SAH treated donor cells compared to controls (60.0 and 40.0% vs. 34.3 and 26.4%, respectively). Moreover, RTA of the 0.5 mM SAH SCNT embryos was significantly (P < 0.05) increased (1.5-fold) in relation to controls. S-adenosyl homocysteine treatment induces global DNA demethylation in donor fibroblasts and enhances the blastocyst frequencies for bovine SCNT embryos that also exhibit greater telomerase activity levels. These results suggest that use of hypomethylated donor somatic cells increases the developmental potential for SCNT embryos by enhancing the nuclear reprogramming efficiency. This work was funded by NSERC, OMAF, OCAG, and CRC.

scholarly journals Identification of a Novel Transcription Factor Binding Element Involved in the Regulation by Differentiation of the Human Telomerase (hTERT) Promoter

2000 ◽  
Vol 11 (12) ◽  
pp. 4381-4391 ◽  
Author(s):  
Maty Tzukerman ◽  
Catherine Shachaf ◽  
Yael Ravel ◽  
Ilana Braunstein ◽  
Orit Cohen-Barak ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Core Promoter ◽  
Embryonic Stem ◽  
Transcription Factor Binding ◽  
Telomerase Activity ◽  
Model Systems ◽  
Time Dependent ◽  
Luciferase Reporter ◽  
Factor Binding ◽  
The Core

Three different cell differentiation experimental model systems (human embryonic stem cells, mouse F9 cells, and human HL-60 promyelocytic cells) were used to determine the relationship between the reduction in telomerase activity after differentiation and the regulation of the promoter for the hTERT gene. Promoter constructs of three different lengths were subcloned into the PGL3-basic luciferase reporter vector. In all three experimental systems, all three promoter constructs drove high levels of reporter activity in the nondifferentiated state, with a marked and time-dependent reduction after the induction of differentiation. In all cases, the smallest core promoter construct (283 nt upstream of the ATG) gave the highest activity. Electrophoretic mobility shift assays revealed transcription factor binding to two E-box domains within the core promoter. There was also a marked time-dependent reduction in this binding with differentiation. In addition, a distinct and novel element was identified within the core promoter, which also underwent time-dependent reduction in transcription factor binding with differentiation. Site-directed mutagenesis of this novel element revealed a correlation between transcription factor binding and promoter activity. Taken together, the results indicate that regulation of overall telomerase activity with differentiation is mediated at least in part at the level of the TERT promoter and provides new information regarding details of the regulatory interactions that are involved in this process.

scholarly journals Tert expression and telomerase activity in gonads and somatic cells of the Japanese medaka (Oryzias latipes)

2008 ◽  
Vol 50 (3) ◽  
pp. 131-141 ◽  
Author(s):  
Frank Pfennig ◽  
Barbara Kind ◽  
Freia Zieschang ◽  
Matthias Busch ◽  
Herwig O. Gutzeit
Keyword(s):  
Somatic Cells ◽  
Oryzias Latipes ◽  
Telomerase Activity ◽  
Japanese Medaka ◽  
Tert Expression

scholarly journals The Catalytic Subunit of DNA-Dependent Protein Kinase Regulates Proliferation, Telomere Length, and Genomic Stability in Human Somatic Cells

2008 ◽  
Vol 28 (20) ◽  
pp. 6182-6195 ◽  
Author(s):  
Brian L. Ruis ◽  
Kazi R. Fattah ◽  
Eric A. Hendrickson
Keyword(s):  
Protein Kinase ◽  
Somatic Cells ◽  
Genomic Stability ◽  
Catalytic Subunit ◽  
Model Systems ◽  
End Joining ◽  
Dependent Protein Kinase ◽  
Exogenous Dna ◽  
Dependent Protein ◽  
Functional Inactivation

ABSTRACT The DNA-dependent protein kinase (DNA-PK) complex is a serine/threonine protein kinase comprised of a 469-kDa catalytic subunit (DNA-PKcs) and the DNA binding regulatory heterodimeric (Ku70/Ku86) complex Ku. DNA-PK functions in the nonhomologous end-joining pathway for the repair of DNA double-stranded breaks (DSBs) introduced by either exogenous DNA damage or endogenous processes, such as lymphoid V(D)J recombination. Not surprisingly, mutations in Ku70, Ku86, or DNA-PKcs result in animals that are sensitive to agents that cause DSBs and that are also immune deficient. While these phenotypes have been validated in several model systems, an extension of them to humans has been missing due to the lack of patients with mutations in any one of the three DNA-PK subunits. The worldwide lack of patients suggests that during mammalian evolution this complex has become uniquely essential in primates. This hypothesis was substantiated by the demonstration that functional inactivation of either Ku70 or Ku86 in human somatic cell lines is lethal. Here we report on the functional inactivation of DNA-PKcs in human somatic cells. Surprisingly, DNA-PKcs does not appear to be essential, although the cell line lacking this gene has profound proliferation and genomic stability deficits not observed for other mammalian systems.

scholarly journals TERT promoter alterations could provide a solution for Peto’s paradox in rodents

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Balázs Vedelek ◽  
Asha Kiran Maddali ◽  
Nurgul Davenova ◽  
Viktor Vedelek ◽  
Imre M. Boros
Keyword(s):  
Transcription Factor ◽  
Tumor Suppressor ◽  
Binding Sites ◽  
Promoter Activity ◽  
Replicative Senescence ◽  
Somatic Cells ◽  
Telomerase Activity ◽  
Cell Number ◽  
Telomere Shortening ◽  
Tert Promoter

AbstractCancer is a genetic disease caused by changes in gene expression resulting from somatic mutations and epigenetic changes. Although the probability of mutations is proportional with cell number and replication cycles, large bodied species do not develop cancer more frequently than smaller ones. This notion is known as Peto’s paradox, and assumes stronger tumor suppression in larger animals. One of the possible tumor suppressor mechanisms involved could be replicative senescence caused by telomere shortening in the absence of telomerase activity. We analysed telomerase promoter activity and transcription factor binding in mammals to identify the key element of telomerase gene inactivation. We found that the GABPA transcription factor plays a key role in TERT regulation in somatic cells of small rodents, but its binding site is absent in larger beavers. Protein binding and reporter gene assays verify different use of this site in different species. The presence or absence of the GABPA TF site in TERT promoters of rodents correlates with TERT promoter activity; thus it could determine whether replicative senescence plays a tumor suppressor role in these species, which could be in direct relation with body mass. The GABPA TF binding sites that contribute to TERT activity in somatic cells of rodents are analogous to those mutated in human tumors, which activate telomerase by a non-ALT mechanism.

scholarly journals Developmental Control of the Cell Cycle: Insights from Caenorhabditis elegans

Genetics ◽  
2019 ◽  
Vol 211 (3) ◽  
pp. 797-829 ◽  
Author(s):  
Edward T. Kipreos ◽  
Sander van den Heuvel
Keyword(s):  
Cell Cycle ◽  
Caenorhabditis Elegans ◽  
Cell Cycle Regulation ◽  
Genetic Model ◽  
Somatic Cells ◽  
Model Systems ◽  
Cell Cycle Regulators ◽  
Animal Development ◽  
C Elegans ◽  
Cycle Regulation

During animal development, a single fertilized egg forms a complete organism with tens to trillions of cells that encompass a large variety of cell types. Cell cycle regulation is therefore at the center of development and needs to be carried out in close coordination with cell differentiation, migration, and death, as well as tissue formation, morphogenesis, and homeostasis. The timing and frequency of cell divisions are controlled by complex combinations of external and cell-intrinsic signals that vary throughout development. Insight into how such controls determine in vivo cell division patterns has come from studies in various genetic model systems. The nematode Caenorhabditis elegans has only about 1000 somatic cells and approximately twice as many germ cells in the adult hermaphrodite. Despite the relatively small number of cells, C. elegans has diverse tissues, including intestine, nerves, striated and smooth muscle, and skin. C. elegans is unique as a model organism for studies of the cell cycle because the somatic cell lineage is invariant. Somatic cells divide at set times during development to produce daughter cells that adopt reproducible developmental fates. Studies in C. elegans have allowed the identification of conserved cell cycle regulators and provided insights into how cell cycle regulation varies between tissues. In this review, we focus on the regulation of the cell cycle in the context of C. elegans development, with reference to other systems, with the goal of better understanding how cell cycle regulation is linked to animal development in general.

scholarly journals Peculiarities of Yeasts and Human Telomerase RNAs Processing

Acta Naturae ◽  
2016 ◽  
Vol 8 (4) ◽  
pp. 14-22 ◽  
Author(s):  
M. P. Rubtsova ◽  
D. P. Vasilkova ◽  
Yu. V. Naraykina ◽  
O. A. Dontsova
Keyword(s):  
Reverse Transcriptase ◽  
Somatic Cells ◽  
Telomerase Activity ◽  
Proliferative Potential ◽  
Telomerase Rna ◽  
Embryonic Cells ◽  
Eukaryotic Chromosome ◽  
Human Telomerase ◽  
Linear Chromosomes

Telomerase is one of the major components of the telomeres -- linear eukaryotic chromosome ends - maintenance system. Linear chromosomes are shortened during each cell division due to the removal of the primer used for DNA replication. Special repeated telomere sequences at the very ends of linear chromosomes prevent the deletion of genome information caused by primer removal. Telomeres are shortened at each replication round until it becomes critically short and is no longer able to protect the chromosome in somatic cells. At this stage, a cell undergoes a crisis and usually dies. Rare cases result in telomerase activation, and the cell gains unlimited proliferative capacity. Special types of cells, such as stem, germ, embryonic cells and cells from tissues with a high proliferative potential, maintain their telomerase activity indefinitely. The telomerase is inactive in the majority of somatic cells. Telomerase activity in vitro requires two key components: telomerase reverse transcriptase and telomerase RNA. In cancer cells, telomerase reactivates due to the expression of the reverse transcriptase gene. Telomerase RNA expresses constitutively in the majority of human cells. This fact suggests that there are alternative functions to telomerase RNA that are unknown at the moment. In this manuscript, we review the biogenesis of yeasts and human telomerase RNAs thanks to breakthroughs achieved in research on telomerase RNA processing by different yeasts species and humans in the last several years.

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