Similar Datasets
Project description:Depletion of growth factors and nutrients induces cellular quiescence, which often accompanies transcriptional silencing and chromatin compaction. Paradoxically, such depletion occurs in pathological microenvironments in which fibroblasts are activated to orchestrate tissue remodeling. The relationship between fibroblast activation and growth factor and nutrient depletion remains unclear. Here, we report that serum depletion in cell culture, a model for growth factor and nutrient depletions, extensively activates transcription in fibroblasts, despite inducing quiescence. Activated genes were enriched for extracellular matrix (ECM) structural components and proteases. The ECM-related transcription accompanied activation of putative distal enhancers, but not promoters. The activated putative enhancers were enriched for non-coding variants associated with inflammatory bowel disease (IBD) risk, suggesting an alteration in the ECM remodeling gene regulatory network in IBD. This study implicates nutrient and growth factor depletion in activating the ECM remodeling gene program in fibroblasts, challenging the prevailing view linking such depletion to transcriptional dormancy.
2025-06-01 | GSE272506 | GEO
Project description:Depletion of growth factors and nutrients induces cellular quiescence, which often accompanies transcriptional silencing and chromatin compaction. Paradoxically, such depletion occurs in pathological microenvironments in which fibroblasts are activated to orchestrate tissue remodeling. The relationship between fibroblast activation and growth factor and nutrient depletion remains unclear. Here, we report that serum depletion in cell culture, a model for growth factor and nutrient depletions, extensively activates transcription in fibroblasts, despite inducing quiescence. Activated genes were enriched for extracellular matrix (ECM) structural components and proteases. The ECM-related transcription accompanied activation of putative distal enhancers, but not promoters. The activated putative enhancers were enriched for non-coding variants associated with inflammatory bowel disease (IBD) risk, suggesting an alteration in the ECM remodeling gene regulatory network in IBD. This study implicates nutrient and growth factor depletion in activating the ECM remodeling gene program in fibroblasts, challenging the prevailing view linking such depletion to transcriptional dormancy.
2025-06-01 | GSE272507 | GEO
Project description:Fibroblast starvation activates ECM remodeling gene transcription and putative enhancers despite inducing quiescence
| PRJNA1262532 | ENA
Project description:Fibroblast starvation activates ECM remodeling gene transcription and putative enhancers despite inducing quiescence [bruseq]
| PRJNA1137061 | ENA
Project description:Fibroblast starvation activates ECM remodeling gene transcription and putative enhancers despite inducing quiescence [chipseq]
| PRJNA1137060 | ENA
Project description:Nutrient deprivation induces a reversible cell cycle arrest state termed quiescence, which often accompanies transcriptional silencing and chromatin compaction. Paradoxically, nutrient deprivation is associated with activated fibroblast states in pathological microenvironments in which fibroblasts drive extracellular matrix (ECM) remodeling to alter tissue environments. The relationship between nutrient deprivation and fibroblast activation remains unclear. Here, we report that serum deprivation extensively activates transcription of ECM remodeling genes in cultured fibroblasts, despite the induction of quiescence. Starvation-induced transcriptional activation accompanied large-scale histone acetylation of putative distal enhancers, but not promoters. The starvation-activated putative enhancers were enriched for non-coding genetic risk variants associated with inflammatory bowel disease (IBD), suggesting that the starvation-activated gene regulatory network may contribute to fibroblast activation in IBD. Indeed, the starvation-activated gene PLAU, encoding uPA serine protease for plasminogen and ECM, was upregulated in inflammatory fibroblasts in the intestines of IBD patients. Furthermore, the starvation-activated putative enhancer at PLAU, which harbors an IBD risk variant, gained chromatin accessibility in IBD patient fibroblasts. This study implicates nutrient deprivation in transcriptional activation of ECM remodeling genes in fibroblasts and suggests nutrient deprivation as a potential mechanism for pathological fibroblast activation in IBD.
| S-EPMC11418948 | biostudies-literature
Project description:Control of synapse number and function in the developing central nervous system is critical to the formation of neural circuits. Astrocytes play a key role in this process by releasing factors that promote the formation of excitatory synapses. Astrocyte-secreted thrombospondins (TSPs) induce the formation of structural synapses, which however remain post-synaptically silent, suggesting that completion of early synaptogenesis may require a two-step mechanism. Here, we show that the humoral innate immune molecule Pentraxin 3 (PTX3) is expressed in the developing rodent brain. PTX3 plays a key role in promoting functionally-active CNS synapses, by increasing the surface levels and synaptic clustering of AMPA glutamate receptors. This process involves tumor necrosis factor-induced protein 6 (TSG6), remodeling of the perineuronal network, and a β1-integrin/ERK pathway. Furthermore, PTX3 activity is regulated by TSP1, which directly interacts with the N-terminal region of PTX3. These data unveil a fundamental role of PTX3 in promoting the first wave of synaptogenesis, and show that interplay of TSP1 and PTX3 sets the proper balance between synaptic growth and synapse function in the developing brain.
| S-EPMC6315291 | biostudies-literature
Project description:The survival of pathogenic fungi in the host after invasion depends on their ability to obtain nutrients, which include the transition metal zinc. This essential micronutrient is required to maintain the structure and function of various proteins and, therefore, plays a critical role in various biological processes. The host's nutritional immunity limits the availability of zinc to pathogenic fungi mainly by the action of calprotectin, a component of neutrophil extracellular traps. Here we investigated the adaptive responses of Fonsecaea pedrosoi to zinc-limiting conditions. This black fungus is the main etiological agent of chromoblastomycosis, a chronic neglected tropical disease that affects subcutaneous tissues. Following exposure to a zinc-limited environment, F. pedrosoi induces a high-affinity zinc uptake machinery, composed of zinc transporters and the zincophore Pra1. A proteomic approach was used to define proteins regulated by zinc deprivation. Cell wall remodeling, changes in neutral lipids homeostasis, and activation of the antioxidant system were the main strategies for survival in the hostile environment. Furthermore, the downregulation of enzymes required for sulfate assimilation was evident. Together, the adaptive responses allow fungal growth and development and reveals molecules that may be related to fungal persistence in the host.
| S-EPMC10890210 | biostudies-literature
Project description:Dynamic regulation of chromatin accessibility is a key feature of cellular differentiation during embryogenesis, but the precise factors that control access to chromatin remain largely unknown. Lsh/HELLS is critical for normal development and mutations of Lsh in human cause the ICF (Immune deficiency, Centromeric instability, Facial anomalies) syndrome, a severe immune disorder with multiple organ deficiencies. We report here that Lsh, previously known to regulate DNA methylation level, has a genome wide chromatin remodeling function. Using micrococcal nuclease (MNase)-seq analysis, we demonstrate that Lsh protects MNase accessibility at transcriptional regulatory regions characterized by DNase I hypersensitivity and certain histone 3 (H3) tail modifications associated with enhancers. Using an auxin-inducible degron system, allowing proteolytical degradation of Lsh, we show that Lsh mediated changes in nucleosome occupancy are independent of DNA methylation level and are characterized by reduced H3 occupancy. While Lsh mediated nucleosome occupancy prevents binding sites for transcription factors in wild type cells, depletion of Lsh leads to an increase in binding of ectopically expressed tissue specific transcription factors to their respective binding sites. Our data suggests that Lsh mediated chromatin remodeling can modulate nucleosome positioning at a subset of putative enhancers contributing to the preservation of cellular identity through regulation of accessibility.
| S-EPMC6557562 | biostudies-literature
Project description:Sulforaphane (SFN) is an isothiocyanate derived from cruciferous vegetables that has demonstrated anti-cancer, anti-microbial and anti-oxidant properties. SFN ameliorates various disease models in rodents (e.g., cancer, diabetes, seizures) that are likewise mitigated by dietary restrictions leading us to test the hypothesis that this compound elicits cellular responses consistent with being a fasting/caloric restriction mimetic. Using immortalized human retinal pigment epithelial cells, we report that SFN impacted multiple nutrient-sensing pathways consistent with a fasted state. SFN treatment (i) increased mitochondrial mass and resistance to oxidative stress, (ii) acutely suppressed markers of mTORC1/2 activity via inhibition of insulin signaling, (iii) upregulated autophagy and further amplified autophagic flux induced by rapamycin or nutrient deprivation while concomitantly promoting lysosomal biogenesis, and (iv) acutely decreased glucose uptake and lactate secretion followed by an adaptive rebound that coincided with suppressed protein levels of thioredoxin-interacting protein (TXNIP) due to early transcriptional down-regulation. This early suppression of TXNIP mRNA expression could be overcome with exogenous glucosamine consistent with SFN inhibiting glutamine F6P amidotransferase, the rate limiting enzyme of the hexosamine biosynthetic pathway. SFN also altered levels of multiple glycolytic and tricarboxylic acid (TCA) cycle intermediates while reducing the inhibitory phosphorylation on pyruvate dehydrogenase, indicative of an adaptive cellular starvation response directing pyruvate into acetyl coenzyme A for uptake by the TCA cycle. RNA-seq of cells treated for 4 h with SFN confirmed the activation of signature starvation-responsive transcriptional programs. Collectively, these data support that the fasting-mimetic properties of SFN could underlie both the therapeutic efficacy and potential toxicity of this phytochemical.
| S-EPMC11758633 | biostudies-literature