Gut-liver axis calibrates intestinal stem cell fitness via PEDF
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA951698 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24055930_1.fastq.gz | Fastqsanger.gz | |||
| SRR24055930_2.fastq.gz | Fastqsanger.gz | |||
| SRR24055931_1.fastq.gz | Fastqsanger.gz | |||
| SRR24055931_2.fastq.gz | Fastqsanger.gz | |||
| SRR24055932_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 34 |
Similar Datasets
Project description:The gut and liver have been recognized to mutually communicate through the biliary tract, portal vein and systemic circulation, but it remains unclear how this gut-liver axis regulates intestinal physiology. Through hepatectomy, transcriptomics and proteomics profiling, we identified pigment epithelium-derived factor (PEDF), as a liver-derived soluble Wnt inhibitor, that can restrain intestinal stem cells (ISC) hyperproliferation for gut homeostasis by competing with Wnt ligands and suppressing Wnt/beta-catenin signaling pathway. In turn, microbial danger signals from intestinal inflammation can be sensed by the liver to repress PEDF production via peroxisome proliferator-activated receptor-alpha (PPAR alpha), liberating ISC proliferation to accelerate tissue repair in the gut. Further, treatment of mice with fenofibrate, a clinical agent of PPARalpha agonist for hypolipidemia enhances the susceptibility of colitis via PEDF activity. Therefore, we identified a distinct role of PEDF to calibrate ISC expansion for intestinal homeostasis via reciprocal interactions between the gut and liver.
2023-03-03 | MSV000091409 | MassIVE
Project description:The gut and liver are recognized to mutually communicate through the biliary tract, portal vein and systemic circulation, but it remains unclear how this gut-liver axis regulates intestinal physiology. Through hepatectomy, transcriptomic and proteomic profiling, we identified pigment epithelium-derived factor (PEDF), a liver-derived soluble Wnt inhibitor, that restrains intestinal stem cell (ISC) hyperproliferation to maintain gut homeostasis by suppressing the Wnt/b-catenin signaling pathway. Further, we found that microbial danger signals occurring as a result of intestinal inflammation can be sensed by the liver to repress PEDF production via peroxisome proliferator-activated receptor-a (PPARa), liberating ISC proliferation to accelerate tissue repair in the gut. Finally, treatment of mice with fenofibrate, a clinical agent of PPARa agonist for hypolipidemia enhances the susceptibility of colitis via PEDF activity. Therefore, we have identified a distinct role for PEDF in calibrating ISC expansion for intestinal homeostasis via reciprocal interactions between the gut and liver.
2024-01-16 | GSE228829 | GEO
Project description:The gut and liver are recognized to mutually communicate through the biliary tract, portal vein, and systemic circulation. However, it remains unclear how this gut-liver axis regulates intestinal physiology. Through hepatectomy and transcriptomic and proteomic profiling, we identified pigment epithelium-derived factor (PEDF), a liver-derived soluble Wnt inhibitor, which restrains intestinal stem cell (ISC) hyperproliferation to maintain gut homeostasis by suppressing the Wnt/β-catenin signaling pathway. Furthermore, we found that microbial danger signals resulting from intestinal inflammation can be sensed by the liver, leading to the repression of PEDF production through peroxisome proliferator-activated receptor-α (PPARα). This repression liberates ISC proliferation to accelerate tissue repair in the gut. Additionally, treating mice with fenofibrate, a clinical PPARα agonist used for hypolipidemia, enhances colitis susceptibility due to PEDF activity. Therefore, we have identified a distinct role for PEDF in calibrating ISC expansion for intestinal homeostasis through reciprocal interactions between the gut and liver.
| S-EPMC10923069 | biostudies-literature
Project description:The development of extra-intestinal diseases is often accompanied by disruptions in intestinal microbiota and their metabolites. Improvement of the intestinal microenvironment frequently results in amelioration of these diseases, highlighting the need to identify key regulatory intestinal factors. In our asthma study, we identified intelectin-1 (ITLN1), predominantly expressed in the intestine, as a critical factor in maintaining intestinal bacterial homeostasis to mitigate allergic asthma via gut-bone-lung axis. We observed that reduced serum ITLN1 levels in asthmatic patients were significantly associated with increased disease severity and airway inflammation. In house dust mite (HDM)-induced asthma mouse model, ITLN1 deficiency exacerbated allergic inflammation by disrupting gut microbial homeostasis, resulting in decreased production of the beneficial short-chain fatty acid butyrate due to reduced Erysipelotrichaceae, Muribaculaceae, and Bifidobacteriaceae levels. Butyrate reduction increased CCL8 secretion by lung macrophages, which facilitated the recruitment of CD4+ T cells from the bone marrow to the lungs through the CCL8-CCR3 axis and enhanced group 2 innate lymphoid cells immune response, thereby amplifying type 2 inflammation. Elevated CCL8 levels were detected in both asthmatic patients and ITLN1-deficient asthmatic mice. Notably, supplementation with either ITLN1 or butyrate, as well as neutralization of CCL8, effectively attenuated lung allergic inflammation and improved asthma outcomes. Our findings establish ITLN1 as a crucial mediator that links gut microbial metabolism to pulmonary immune regulation, providing insights into the gut-bone-lung axis as a regulatory mechanism in asthma pathogenesis. These results position ITLN1 as a promising therapeutic target for modulating the intestinal microenvironment and mitigating systemic inflammatory responses in asthma and related disorders.
2025-12-09 | GSE281643 | GEO
Project description:We demonstrated that Lepr+ mesenchymal cells surround intestinal crypts where ISCs and transit-amplifying (TA) cells localize. The abundance of these cells increased upon administration of a high-fat diet (HFD) but dramatically decreased upon fasting. Depletion of Lepr+ mesenchymal cells resulted in fewer ISCs, compromised architecture of crypt-villi axis and impaired intestinal regeneration. Furthermore, Lepr+ cell-derived Igf1 has been identified as an important effector that promotes the proliferation of ISCs and TA cells. Deletion of Igf1 in Lepr+ cells partially recapitulated Lepr+ cell-ablated intestinal phenotypes during both homeostasis and regeneration. Overall, Lepr+ mesenchymal cells sense diet alteration and function as a novel niche for ISCs via the stromal Igf1 - epithelial Igf1r axis, which is critical for intestinal homeostasis and regeneration. These findings revealed that Lepr+ mesenchymal cells are an important mediator that links diet to ISC function and might provide a novel therapeutic target for gut diseases.
2022-03-07 | GSE165806 | GEO
Project description:A central hallmark of brain aging is the alteration of neuronal functions in the hippocampus, leading to a progressive decline in learning and memory. Multiple reports have shown the importance of blood-borne factors in inter-tissue communication for the maintenance of cognitive fitness and proper regulation of neuronal homeostasis throughout life. Among these blood-borne factors, we identified Osteocalcin (OCN), a bone-derived hormone. OCN induces autophagy machinery in hippocampal neurons which is essential for activity-dependent synaptic plasticity. However, the way in which blood-borne factors like OCN communicate with neurons, including their regulatory mechanisms, remains largely elusive. Here, we show the importance of a core primary cilium (PC)-proteins/autophagy machinery axis in hippocampal neurons that mediate the effects of the pro-youthful blood factor OCN on neuronal homeostasis and cognitive fitness. We found that OCN’s receptor, GPR158, is present at the PC of hippocampal neurons and mediates the regulation of autophagy machinery by OCN. During aging, PC-core proteins are reduced in hippocampal neurons and associated with neuronal PC morphological abnormalities. Restoring their levels is sufficient to improve neuronal autophagy and cognitive impairments in aged mice. Mechanistically, we found that OCN promotes neuronal autophagy in the hippocampus by the induction of PC-dependent cAMP response element-binding protein (CREB) signaling pathway. Altogether, this study proposes a novel paradigm for blood factor-neuron communication dependent on a neuronal PC/autophagy axis by identifying a novel regulatory pathway fostering cognitive fitness and providing the foundation for autophagy-based therapeutic strategies to treat age-related cognitive dysfunction.
2024-11-07 | PXD056975 | Pride
Project description:The mechanisms that mediate inflammatory macrophages in intestinal inflammation are incompletely understood. Here, using merged analysis of RNA sequences and mass spectrometry (MS)-based quantitative proteomics, we report the distinction of proteomics and transcriptomics in activated macrophage. Dipeptidase-2 (DPEP2), belonging to DPEP family, is highly expressed and downregulated sharply at protein level but not mRNA level in macrophages responding to inflammatory stimulations. Repression of DPEP2 not only enhances macrophage-mediated intestinal inflammation in vivo but also promotes the production of ROS and the transduction of inflammatory pathways in macrophages in vitro. Mechanistically, DPEP2 inhibits recruitment of inactivated macrophages to inflammatory sites by impairing activation of vimentin (VIM), and DPEP2 downregulation promotes the infiltration of pro-inflammatory macrophages through enhancing the activation of VIM by Akt1. Besides, overexpressed DPEP2 inhibits the transduction of inflammatory signals by resisting MAK3K7 in inactivated macrophages, and DPEP2 is degraded by activated Trim32 resulting in sharp activation of NF-κB and p38 MAPK signals by released MAK3K7 in pro-inflammatory macrophages during the development of intestinal inflammation. Trim32-DPEP2 axis accumulates potential energy of inflammation for macrophages. These results identify DPEP2 as a key regulator of macrophage-mediated intestinal inflammation. Thus, Trim32-DPEP2 axis may be a potential therapeutic target for intestinal inflammation.
2025-07-28 | PXD057405 | Pride
Project description:Genes encoding transcription factors function as hubs in gene regulatory networks because they encode DNA-binding proteins, which bind to promoters that carry their binding sites. In the present work we have studied gene regulatory networks defined by genes with transcripts belonging to different mRNA abundance classes in the small intestinal epithelial cell. The focus is the rewiring that occurs in transcription factor hubs in these networks during the differentiation of the small intestinal epithelial cell while it migrates along the crypt-villus axis and during its development from a fetal endodermal cell to a mature adult villus epithelial cell. We have generated transcriptome data for mouse small intestinal villus, crypt and fetal intestinal epithelial cells. In addition we have generated metabolome data from crypt and villus cells. Our results show that the intestinal crypt transcription factor hubs that are rewired during differentiation are involved in the cell cycle process (E2F, NF-Y) and stem cell maintenance (c-Myc). In contrast the villi are dominated by a HNF-4 villus hub, which is rewired during differentiation by the addition of network genes with relevance for lipoprotein synthesis and lipid absorption. Moreover, we have identified a villus NF-kB hub, which was revealed by comparison of the villus and endoderm transcriptomes. The rewiring of the NF-kB villus hub during intestinal development reflects transcriptional activity established by host and microflora interactions. To aid in the mining of our results we have developed a web portal (http://gastro.imbg.ku.dk/mousecv/) allowing easy linkage between the transcriptomic data, biological processes and functions. Experiment Overall Design: Four different sample categories were analyzed. Experiment Overall Design: 1) Small intestinal crypts isolated form 12-weeks old C57BL/6 mice. These samples are in triplicates. Experiment Overall Design: 2) Small intestinal villi isolated form 12-weeks old C57BL/6 mice. These samples are in triplicates. Experiment Overall Design: 3) Embryonic day 12 mesenchyme. These samples are in quadruplicate. each sample is derived from a pool of mesenchymes (10-40) Experiment Overall Design: 4) Embryonic day 12 endoderm. These samples are in quadruplicate. each sample is derived from a pool of endoderms (10-40)
2008-06-12 | E-GEOD-3216 | biostudies-arrayexpress
Project description:Intestinal epithelial cells (IECs) are pivotal for maintaining intestinal homeostasis through self-renewal, proliferation, differentiation, and regulated cell death. While apoptosis and necroptosis are recognized as distinct pathways, their intricate interplay remains elusive. In this study, we report that Mettl3-mediated m6A modification maintains intestinal homeostasis by impeding epithelial cell death. Mettl3 knockout induces both apoptosis and necroptosis in IECs. Targeting different modes of cell death with specific inhibitors unveils that RIPK1 kinase activity is critical for the cell death triggered by Mettl3 knockout. Mechanistically, this occurs via the m6A-mediated transcriptional regulation of Atf3, a transcription factor that directly binds to Cflar, the gene encoding the anti-cell death protein cFLIP. cFLIP inhibits RIPK1 activity, thereby suppressing downstream apoptotic and necroptotic signaling. Together, these findings delineate the essential role of the METTL3-ATF3-cFLIP axis in homeostatic regulation of the intestinal epithelium by blocking RIPK1 activity.
2024-09-05 | GSE262282 | GEO
Project description:Propionate axis in infancy small intestinal eosinophils
| PRJNA856863 | ENA