Gene expression profiling of stress-induced senescence and paracrine senecence in human hepatocytes
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE210140 | GEO | 2024/09/01
REPOSITORIES: GEO
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Project description:Cellular senescence can be transmitted to neighbouring cells in a paracrine manner through different mechanisms, including soluble factors released by senescent cells. To understand the dynamic regulation of paracrine senescence, here we investigated gene expression profiles in normal human fibroblasts (IMR90) exposed to conditioned medium generated by an inducible model of fibroblast Oncogene-Induced Senescence (IMR90-ER:RAS) at different time points after induction of senescence.
2022-04-05 | GSE139563 | GEO
Project description:Senescence can be transmitted in a paracrine way from cells undergoing Oncogene Induced Senescence (OIS) to naïve normal cells. We define this phenomenon as “paracrine senescence” We used microarrays to compare the trancriptome of cells undergoing paracrine senescence to the transcriptome of cells suffering OIS to unveil the common signatures defining both events and the similarities between them
2013-06-13 | GSE41318 | GEO
Project description:Senescence can be transmitted in a paracrine way from cells undergoing Oncogene Induced Senescence (OIS) to naM-CM-/ve normal cells. We define this phenomenon as M-bM-^@M-^\paracrine senescenceM-bM-^@M-^] We used microarrays to compare the trancriptome of cells undergoing paracrine senescence to the transcriptome of cells suffering OIS to unveil the common signatures defining both events and the similarities between them IMR90 cells were co-cultured with IMR90 ER:RAS undergoing OIS or IMR90-Vector control cells using 0.2 M-NM-<m pore transwell (anopore) to allow communication of soluble factors but physical separation of the two cell populations. The total mRNA of IMR90, IMR90 ER:RAS or IMR90 cells cultured in Transwells together with IMR90 vector or IMR90 ER:RAS cells during 7 days in the presence of 200 nM 4OHT and 0.5 % FBS was extracted and hybridized on Affymetrix microarrays to compare paracrine senescence to OIS.
2013-06-13 | E-GEOD-41318 | biostudies-arrayexpress
Project description:Human Cardiac/Progenitod Stem Cells (hCSCs) transplantation is arising as a novel therapy option for acute myocardial infarction (AMI) patients. The majority of the studies reported point to paracrine signaling as the main effector in hCSCs activation and regenerative capacity. However, the mechanisms of action of these cells in response to AMI paracrine context are still poorly understood. In the present study, a quantitative proteomics analysis (SWATH-MS) was employed to investigate hCSC response to paracrine factors released by human cardiomyocytes (hCMs) in response to an in vitro AMI Ischemia/Reperfusion (I/R) injury. A total of 714 proteins were quantified, from which 86 were differentially expressed, including 63 proteins up-regulated and 23 down-regulated in hCSCs exposed to hCM I/R injury conditioned media vs hCSCs exposed to control hCM conditioned media. Bioinformatics functional analysis revealed up-regulation of proteins involved with endocytosis, paracrine signaling, proliferation, migration and stress response. This work provides an insight into hCSC biology in response to paracrine cues derived from hCMs upon I/R injury, and the data generated herein constitutes a rich resource for further studies aiming at potentiating the regenerative properties of these cells.
2019-09-25 | PXD011998 | Pride
Project description:To study the effect of myoblast-derived paracrine factors on cardiomyocyte gene expression, microarray analysis was performed from isolated rat fetal cardiomyocyte cultures. These cultures were treated for 24 hours with fresh culture medium (control), skeletal myoblast-conditioned medium, or cardiac fibroblast-conditioned medium. In total, 3 samples were analyzed.
2012-01-28 | E-GEOD-35393 | biostudies-arrayexpress
Project description:Senescence, the irreversible cell cycle arrest of damaged cells, is accompanied by a deleterious pro-inflammatory senescence-associated secretory phenotype (SASP). Senescence and the SASP are major factors in aging, cancer, and degenerative diseases, and interfere with the expansion of adult cells in vitro, yet little is known about how to counteract their induction and deleterious effects. Paracrine signals are increasingly recognized as important senescence triggers and understanding their regulation and mode of action may provide novel opportunities to reduce senescence-induced inflammation and improve cell-based therapies. Here, we show that the signalling protein WNT3A counteracts senescence in cultured human adult multipotent stromal cells (MSCs) by limiting paracrine senescence. We find that entry into senescence in a small subpopulation of MSCs triggers a secretome that causes a feed-forward signalling cascade that with increasing speed induces healthy cells into senescence. WNT signals interrupt this cascade by repressing cytokines that mediate this induction of senescence. Inhibition of those mediators by interference with NF-kB or interleukin 6 signalling reduced paracrine senescence in absence of WNT3A and promoted the expansion of MSCs. Our work reveals how WNT signals can antagonize senescence and has relevance not only for expansion of adult cells but can also provide new insights into senescence-associated inflammatory and degenerative diseases. // The RNAseq data in particular focusses on the transcriptome changes in MSCs occuring in vitro culture over four passages in presence or absence of growth factors WNT3A and FGF2.
2021-11-24 | GSE152112 | GEO
Project description:To study the effect of myoblast-derived paracrine factors on cardiomyocyte gene expression, microarray analysis was performed from isolated rat fetal cardiomyocyte cultures. These cultures were treated for 24 hours with fresh culture medium (control), skeletal myoblast-conditioned medium, or cardiac fibroblast-conditioned medium.
2012-01-28 | GSE35393 | GEO
Project description:We are here presenting a new paracrine induction of RNA granules by viruses. Infection by viruses imposes major stress on the host cell. In response to this stress, infected cells can induce several defence mechanisms, which include the activation of stress response pathways and the innate immune response. These often result in an inhibition of translation culminating in the assembly of cytoplasmic granules called stress granules (SGs). SGs assembly follows from liquid phase separation of aggregation-prone proteins such G3BP1 and TIA-1, leading to the sequestration of mRNAs. Because this threatens viral gene expression, viruses need to evade these stress response pathways to propagate. Using feline calicivirus (FCV), surrogate for norovirus, the main virus responsible for gastroenteritis outbreaks worldwide, we previously showed that FCV impairs SGs assembly by cleaving the scaffold protein G3BP1. Interestingly, we observed that uninfected bystander cells assembled G3BP1 granules, suggesting a paracrine response trigged by the infection. We now present evidence that virus-free supernatant generated from infected cells can induce the formation of RNA granules. We have characterised the dynamic of the granules assembly via confocal microscopy. Moreover, we provide an understanding of paracrine granules function and specificity through their affinity purification followed by proteomics and RNAseq analysis of their proteins and mRNAs content. This helps to define rules of assembly and novel functions for paracrine granules highlighting fundamental differences with canonical stress granules.
2022-03-14 | PXD021881 | Pride
Project description:Background: Senescent hepatocytes accumulate in parallel with fibrosis progression during NASH. The mechanisms that enable progressive expansion of nonreplicating cell populations and the significance of that process in determining NASH outcomes are unclear. Many types of senescing cells upregulate the THBD-PAR-1 signaling axis to remain viable. Vorapaxar, an FDA-approved PAR-1 inhibitor, blocks the activity of that pathway. We used vorapaxar to determine if and how THBD-PAR1 signaling promotes fibrosis progression in NASH. Methods: We evaluated the THBD-PAR1 pathway in liver biopsies from NAFLD patient cohorts with a spectrum of liver fibrosis. Chow fed mice were treated with viral vectors to over-express p16 specifically in hepatocytes and induce replicative senescence. Effects on the THBD-PAR-1 axis and regenerative capacity were assessed; the transcriptome of p16 over-expressing hepatocytes was characterized and we examined how conditioned medium from senescent but viable (dubbed ‘undead’) hepatocytes reprograms hepatic stellate cells. A genetically obese mouse model of NASH with little liver fibrosis, and a diet-induced mouse model of NASH with advanced fibrosis were treated with vorapaxar to determine effects on hepatocyte senescence and liver damage. Results: Inducing senescence up-regulates the THBD-PAR1 signaling axis in hepatocytes and induces their expression of fibrogenic factors, including hedgehog ligands. Hepatocyte THBD-PAR1 signaling increases in NAFLD and supports sustained hepatocyte senescence that limits effective liver regeneration and promotes maladaptive repair. Inhibiting PAR-1 signaling with vorapaxar interrupts this process, reduces the burden of ‘undead’ senescent cells, and safely improves NASH and fibrosis despite ongoing lipotoxic stress Conclusion: The THBD-PAR1 signaling axis is a novel therapeutic target for NASH because blocking this pathway prevents accumulation of senescing but viable hepatocytes that generate factors that promote maladaptive liver repair.
2023-03-01 | GSE204901 | GEO
Project description:The aging of pancreatic beta-cells may undermine their ability to compensate for insulin resistance, leading to the development of type 2 diabetes (T2D). Aging beta-cells acquire markers of cellular senescence and develop a senescence-associated secretory phenotype (SASP) that can lead to senescence and dysfunction of neighboring cells through paracrine actions, contributing to beta-cell failure. Herein, we defined the beta-cell SASP signature based on unbiased proteomic analysis of conditioned media of cells obtained from human senescent beta-cells. These experiments revealed that the beta-cell SASP is enriched for factors associated with inflammation, cellular stress response, and extracellular matrix remodeling across species.
2021-03-18 | GSE162521 | GEO