Similarities in Gene Expression Profiles during<i>In Vitro</i>Aging of Primary Human Embryonic Lung and Foreskin Fibroblasts

Marthandan, Shiva; Priebe, Stefan; Baumgart, Mario; Groth, Marco; Cellerino, Alessandro; Guthke, Reinhard; Hemmerich, Peter; Diekmann, Stephan

doi:10.1155/2015/731938

Cited by 41 publications

(57 citation statements)

References 89 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We selected five different fibroblast cell strains (MRC-5, BJ, IMR-90, WI-38 and HFF) and monitored their replicative behavior during passaging into senescence. The similarities in gene expression profiles of primary human fibroblast strains derived from embryonic lung and foreskin were revealed by us previously [ 76 ]. We extended our previous study [ 76 ] with data obtained from further three fibroblast strains (BJ, IMR-90 and WI-38) in this study in order to essentially extend the statistical basis for deducing common age-driven changes in the transcriptome.…”

Section: Resultsmentioning

confidence: 81%

“…The similarities in gene expression profiles of primary human fibroblast strains derived from embryonic lung and foreskin were revealed by us previously [ 76 ]. We extended our previous study [ 76 ] with data obtained from further three fibroblast strains (BJ, IMR-90 and WI-38) in this study in order to essentially extend the statistical basis for deducing common age-driven changes in the transcriptome. In our analysis, the cell strains were derived from a single vial and were maintained in culture as triplicates from an early population doubling (PD) time point until they achieved senescence at late PDs ( Fig 1A ).…”

Section: Resultsmentioning

confidence: 81%

See 1 more Smart Citation

Conserved Senescence Associated Genes and Pathways in Primary Human Fibroblasts Detected by RNA-Seq

et al. 2016

View full text Add to dashboard Cite

Cellular senescence correlates with changes in the transcriptome. To obtain a complete view on senescence-associated transcription networks and pathways, we assessed by deep RNA sequencing the transcriptomes of five of the most commonly used laboratory strains of human fibroblasts during their transition into senescence. In a number of cases, we verified the RNA-seq data by real-time PCR. By determining cellular protein levels we observed that the age-related expression of most but not all genes is regulated at the transcriptional level. We found that 78% of the age-affected differentially expressed genes were commonly regulated in the same direction (either up- or down-regulated) in all five fibroblast strains, indicating a strong conservation of age-associated changes in the transcriptome. KEGG pathway analyses confirmed up-regulation of the senescence-associated secretory phenotype and down-regulation of DNA synthesis/repair and most cell cycle pathways common in all five cell strains. Newly identified senescence-induced pathways include up-regulation of endocytotic/phagocytic pathways and down-regulation of the mRNA metabolism and the mRNA splicing pathways. Our results provide an unprecedented comprehensive and deep view into the individual and common transcriptome and pathway changes during the transition into of senescence of five human fibroblast cell strains.

show abstract

Section: Resultsmentioning

confidence: 81%

Section: Resultsmentioning

confidence: 81%

Conserved Senescence Associated Genes and Pathways in Primary Human Fibroblasts Detected by RNA-Seq

et al. 2016

View full text Add to dashboard Cite

show abstract

“…HIV-1 and MLV integration sites in HEK293T cells alongside the matched random control simulated data were from published work (11). HT1080, HEK293T, MRC5, or HepG2 cell line-specific gene-expression activity was reported previously (GEO accession codes GSE58968, GSE11892, GSE63577, and GSE87958) (54)(55)(56)(57). All observable differences between WT and the corresponding mutant data were statistically significant (P < 0.05) (Dataset S1).…”

Section: Methodsmentioning

confidence: 99%

Structural basis for spumavirus GAG tethering to chromatin

Lesbats

Serrao

Maskell

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The interactions between a retrovirus and host cell chromatin that underlie integration and provirus expression are poorly understood. The prototype foamy virus (PFV) structural protein GAG associates with chromosomes via a chromatin-binding sequence (CBS) located within its C-terminal region. Here, we show that the PFV CBS is essential and sufficient for a direct interaction with nucleosomes and present a crystal structure of the CBS bound to a mononucleosome. The CBS interacts with the histone octamer, engaging the H2A-H2B acidic patch in a manner similar to other acidic patch-binding proteins such as herpesvirus latency-associated nuclear antigen (LANA). Substitutions of the invariant arginine anchor residue in GAG result in global redistribution of PFV and macaque simian foamy virus (SFV mac ) integration sites toward centromeres, dampening the resulting proviral expression without affecting the overall efficiency of integration. Our findings underscore the importance of retroviral structural proteins for integration site selection and the avoidance of genomic junkyards.retrovirus | integration | nucleosome | chromatin-binding

show abstract

“…GSE53330; E-MTAB-4879; and refs. [35][36][37][38][39][40][41][42][43][44] ). In 21 out of 25 datasets spanning a range of tissues, we detected an elevation of cryptic transcription with age ( Figure S2), similar to what was observed in the stem cells.…”

Section: Analysis Of Rna-seq Data Indicates An Increase Of Intragenicmentioning

confidence: 99%

Age-associated cryptic transcription in mammalian stem cells is linked to permissive chromatin at cryptic promoters

McCauley¹,

Sun²,

Yu³

et al. 2020

Preprint

View full text Add to dashboard Cite

Suppressing spurious cryptic transcription by a repressive intragenic chromatin state featuring trimethylated lysine 36 on histone H3 (H3K36me3) and DNA methylation is critical for maintaining self-renewal capacity in mouse embryonic stem cells. In yeast and nematodes, such cryptic transcription is elevated with age, and reducing the levels of age-associated cryptic transcription extends yeast lifespan. Whether cryptic transcription is also increased during mammalian aging is unknown. We show for the first time an age-associated elevation in cryptic transcription in several stem cell populations, including murine hematopoietic stem cells (mHSCs) and neural stem cells (NSCs) and human mesenchymal stem cells (hMSCs). Using DECAP-seq, we mapped and quantified age-associated cryptic transcription in hMSCs aged in vitro. Regions with significant age-associated cryptic transcription have a unique chromatin signature: decreased H3K36me3 and increased H3K4me1, H3K4me3, and H3K27ac with age. Furthermore, genomic regions undergoing such age-dependent chromatin changes resemble known promoter sequences and are bound by the promoter-associated protein TBP even in young cells. Hence, the more permissive chromatin state at intragenic cryptic promoters likely underlies the increase of cryptic transcription in aged mammalian stem cells.

show abstract

Similarities in Gene Expression Profiles duringIn VitroAging of Primary Human Embryonic Lung and Foreskin Fibroblasts

Cited by 41 publications

References 89 publications

Conserved Senescence Associated Genes and Pathways in Primary Human Fibroblasts Detected by RNA-Seq

Conserved Senescence Associated Genes and Pathways in Primary Human Fibroblasts Detected by RNA-Seq

Structural basis for spumavirus GAG tethering to chromatin

Age-associated cryptic transcription in mammalian stem cells is linked to permissive chromatin at cryptic promoters

Contact Info

Product

Resources

About