Rapamycin reduces fibroblast proliferation without causing quiescence and induces STAT5A/B-mediated cytokine production

Gillespie, Zoe E.; MacKay, Kimberly; Sander, Michelle Y.; Trost, Brett; Dawicki, Wojciech; Wickramarathna, Aruna D.; Gordon, John; Eramian, Mark; Kill, Ian R.; Bridger, Joanna M.; Kusalik, Anthony; Mitchell, Jennifer A.; Eskiw, Christopher H.

doi:10.1080/19491034.2015.1128610

Cited by 18 publications

(35 citation statements)

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“…We previously performed comparative transcriptome analysis of RNA-seq datasets to identify genes that had changed expression more than or equal to fivefold as fibroblasts were induced from proliferative growth to quiescence using serum starvation [ 19 ]. Our analyses demonstrated that 751 genes (not probes) changed expression (428 increased and 323 decreased), and that these genes could be mapped to specific biological pathways, including cell cycle control and mitosis, as well as the complement and coagulation cascade.…”

Section: Resultsmentioning

confidence: 99%

Concordance between RNA-sequencing data and DNA microarray data in transcriptome analysis of proliferative and quiescent fibroblasts

et al. 2015

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DNA microarrays and RNA sequencing (RNA-seq) are major technologies for performing high-throughput analysis of transcript abundance. Recently, concerns have been raised regarding the concordance of data derived from the two techniques. Using cDNA libraries derived from normal human foreskin fibroblasts, we measured changes in transcript abundance as cells transitioned from proliferative growth to quiescence using both DNA microarrays and RNA-seq. The internal reproducibility of the RNA-seq data was greater than that of the microarray data. Correlations between the RNA-seq data and the individual microarrays were low, but correlations between the RNA-seq values and the geometric mean of the microarray values were moderate. The two technologies had good agreement when considering probes with the largest (both positive and negative) fold change (FC) values. An independent technique, quantitative reverse-transcription PCR (qRT-PCR), was used to measure the FC of 76 genes between proliferative and quiescent samples, and a higher correlation was observed between the qRT-PCR data and the RNA-seq data than between the qRT-PCR data and the microarray data.

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Section: Resultsmentioning

confidence: 99%

Concordance between RNA-sequencing data and DNA microarray data in transcriptome analysis of proliferative and quiescent fibroblasts

et al. 2015

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“…Rapamycin has been extensively linked to cytokine expression and regulation across multiple cell lines. In healthy human foreskin fibroblasts [2DD], rapamycin caused up-regulation of numerous genes, including cytokine genes from the IL-6 signaling cascade, such as IL-6, IL-8, IL-11 , and leukemia inhibitory factor (LIF ; Gillespie et al, 2015 ). Analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway terms identified a specific enrichment of cytokine-cytokine receptor interactions.…”

Section: Rapamycinmentioning

confidence: 99%

“…Analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway terms identified a specific enrichment of cytokine-cytokine receptor interactions. Furthermore, transcription factor motif searches of up-regulated promoters and subsequent chromatin immuno-precipitation (ChIP) analyses demonstrated STAT5A/B as likely mediating rapamycin-induced changes in gene expression (Gillespie et al, 2015 ). Compounds that activate SIRT1 function suppress pSTAT5A/B signaling in response to IL-2 and decrease mouse and human T-cell proliferation (Gardner et al, 2013 ).…”

Section: Rapamycinmentioning

confidence: 99%

Better Living through Chemistry: Caloric Restriction (CR) and CR Mimetics Alter Genome Function to Promote Increased Health and Lifespan

2016

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Caloric restriction (CR), defined as decreased nutrient intake without causing malnutrition, has been documented to increase both health and lifespan across numerous organisms, including humans. Many drugs and other compounds naturally occurring in our diet (nutraceuticals) have been postulated to act as mimetics of caloric restriction, leading to a wave of research investigating the efficacy of these compounds in preventing age-related diseases and promoting healthier, longer lifespans. Although well studied at the biochemical level, there are still many unanswered questions about how CR and CR mimetics impact genome function and structure. Here we discuss how genome function and structure are influenced by CR and potential CR mimetics, including changes in gene expression profiles and epigenetic modifications and their potential to identify the genetic fountain of youth.

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“…The red circles in panels B and D represent the genomic regions involved in an interaction. demonstrated in a wide variety of cellular processes, including differentiation [31], serum response [39], therapeutic response [21,40] and response to DNA damage [41]. The unique spatial organization of the genome that is seen under these different cellular conditions is hypothesized to be a crucial mechanism driving various nuclear and cellular functions.…”

Section: Introductionmentioning

confidence: 99%

“…B1 < B2 , 19 ( member ( Chr1 , Set1 ) , member ( Chr2 , Set2 ) -> true 20 ; member ( Chr1 , Set2 ) , member ( Chr2 , Set1 ) -> true 21 ) , 22 assertz ( edge ( B1 , B2 , F )) ,…”

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confidence: 99%

SonHi-C: a set of non-procedural approaches for predicting 3D genome organization from Hi-C data

MacKay

Carlsson²,

Kusalik

2018

Preprint

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Background: Many computational methods have been developed that leverage the results from biological experiments (such as Hi-C) to infer the 3D organization of the genome.Formally, this is referred to as the 3D genome reconstruction problem (3D-GRP). None of the existing methods for solving the 3D-GRP have utilized a non-procedural programming approach (such as constraint programming or integer programming) despite the established advantages and successful applications of such approaches for predicting the 3D structure of other biomolecules. Our objective was to develop a set of mathematical models and corresponding non-procedural implementations for solving the 3D-GRP to realize the same advantages.Results: We present a set of non-procedural approaches for predicting 3D genome organization from Hi-C data (collectively referred to as SonHi-C and pronounced "sonic").Specifically, this set is comprised of three mathematical models based on constraint programming (CP), graph matching (GM) and integer programming (IP). All of the mathematical models were implemented using non-procedural languages and tested with Hi-C data from Schizosaccharomyces pombe (fission yeast). The CP implementation could not optimally solve the problem posed by the fission yeast data after several days of execution time. The . CC-BY-NC 4.0 International license It is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/392407 doi: bioRxiv preprint first posted online Aug. 16, 2018; GM and IP implementations were able to predict a 3D model of the fission yeast genome in 1.088 and 294.44 seconds, respectively. These 3D models were then biologically validated through literature search which verified that the predictions were able to recapitulate key documented features of the yeast genome.Conclusions: Overall, the mathematical models and programs developed here demonstrate the power of non-procedural programming and graph theoretic techniques for quickly and accurately modelling the 3D genome from Hi-C data. Additionally, they highlight the practical differences observed when differing non-procedural approaches are utilized to solve the 3D-GRP.Key Words: 3D Genome Reconstruction Problem, Mathematical Modelling, Constraint Programming, Graph Matching, Integer Programming BackgroundWithin the nucleus, a cell's genetic information undergoes extensive folding and reorganization throughout normal physiological processes. Just like in origami where the same piece of paper folded in different ways allows the paper to take on different forms and potential functions, it is possible that different genomic organizations are related to various nuclear functions. Until recently, it has been extremely difficult to comprehensively investigate this relationship due to the lack of high-resolution and high-throughput techniques for identifying genomic organizations. The development of a techn...

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Rapamycin reduces fibroblast proliferation without causing quiescence and induces STAT5A/B-mediated cytokine production

Cited by 18 publications

References 59 publications

Concordance between RNA-sequencing data and DNA microarray data in transcriptome analysis of proliferative and quiescent fibroblasts

Concordance between RNA-sequencing data and DNA microarray data in transcriptome analysis of proliferative and quiescent fibroblasts

Better Living through Chemistry: Caloric Restriction (CR) and CR Mimetics Alter Genome Function to Promote Increased Health and Lifespan

SonHi-C: a set of non-procedural approaches for predicting 3D genome organization from Hi-C data

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