Single-cell transcriptomics predict novel potential regulators of acute epithelial restitution in the ischemia-injured intestine
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PROVIDER: PRJNA1129556 | ENA |
REPOSITORIES: ENA
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Project description:This original research article outlines the successful isolation and characterization of the transcriptomic profile of post-ischemic restituting epithelial through a translational pig model.
2025-07-02 | GSE271071 | GEO
Project description:Ischemic damage to the intestinal epithelial barrier, such as in necrotizing enterocolitis or small intestinal volvulus, is associated with higher mortality rates in younger patients. We have recently reported a powerful pig model to investigate these age-dependent outcomes in which mucosal barrier restitution is strikingly absent in neonates but can be rescued by direct application of homogenized mucosa from older, juvenile pigs by a yet-undefined mechanism. Within the mucosa, a postnatally developing network of enteric glial cells (EGC) is gaining recognition as a key regulator of the mucosal barrier. Therefore, we hypothesized that the developing EGC network may play an important role in coordinating intestinal barrier repair in neonates. Neonatal and juvenile jejunal mucosa recovering from surgically induced intestinal ischemia was visualized by scanning electron microscopy and the transcriptomic phenotypes were assessed by bulk RNA sequencing. EGC network development was examined by gene set enrichment analysis, three-dimensional volume imaging and western blot and its function in regulating epithelial restitution assessed ex vivo in Ussing chamber using the glia-specific inhibitor fluoroacetate, and in vivo in co-culture assays. Here we refine and elaborate our translational model, confirming a neonatal phenotype characterized by a complete lack of coordinated reparative signaling in the mucosal microenvironment. Further, we report important evidence that the subepithelial EGC network changes significantly over the early postnatal period and demonstrate that EGC function in close proximity to wounded intestinal epithelium is critical to intestinal barrier restitution following ischemic injury.
2022-09-08 | GSE212533 | GEO
Project description:Background and Purpose: Long noncoding RNAs (lncRNAs) are an emerging class of genomic regulatory molecules reported in neurodevelopment and many diseases. Despite extensive studies have identified lncRNAs and discovered their functions in CNS diseases, the function of lncRNAs in ischemia stroke remains poorly understood. Method: Ischemia was induced by transient middle cerebral artery occlusion. Expression profiles of lncRNAs, miRNAs and mRNAs after ischemia stroke were obtained using high throughput sequencing technology. A correlation network was constructed to predict lncRNA functions. LncRNA-miRNA-mRNA network was constructed to discover ceRNAs. Results: 1924 novel lncRNAs were identified, indicating that the ischemia stroke has a complex effect on lncRNAs. The top 10 regulated lncRNAs was validated by qRT-PCR. We have also predicted function of lncRNAs, and subjected them to gene co-expression network analysis, revealing the involvement of lncRNAs in many important biological process including injury and repair that are implicated in the regulation of ischemia stroke. Furthermore, lncRNAs mediated SMD (Staufen1-mediated mRNA decay) was analyzed and ceRNA (competitive endogenous RNAs) network was constructed in ischemia stroke. Conclusions: This study reports the genome-wide lncRNA profiles in ischemia stroke using high throughput sequencing and constructs a systematic lncRNA-miRNA-mRNA network which reveals a complex functional noncoding RNA regulatory network in ischemia stroke.
2017-02-23 | GSE78200 | GEO
Project description:Restitution of the extrahepatic biliary luminal epithelium in cholangiopathies is poorly understood. Prominin-1 (Prom1) is a key component of epithelial ciliary body of stem/progenitor cells. Given that intrahepatic Prom1-expressing progenitor cells undergo cholangiocyte differentiation, we hypothesized that Prom1 may promote restitution of the extrahepatic bile duct (EHBD) epithelium following injury. Utilizing various murine biliary injury models, we identified Prom1-expressing cells in the peribiliary glands (PBGs) of the EHBD. These Prom1-expressing cells are progenitor cells which give rise to cholangiocytes as part of the normal maintenance of the EHBD epithelium. Following injury, these cells proliferate significantly more rapidly to re-populate the biliary luminal epithelium. Null mutation of Prom1 leads to significantly more than ten-fold dilated PBGs following rhesus rotavirus-mediated biliary injury. Cultured organoids derived from Prom1 knockout mice are comprised of biliary progenitor cells with altered apical-basal cellular polarity, significantly fewer and shorter cilia, and decreased organoid proliferation dynamics consistent with impaired cell motility. We, therefore, conclude that Prom1 is involved in biliary epithelial restitution following biliary injury in part through its role in supporting cell polarity.
2022-12-05 | GSE220054 | GEO
Project description:Bleomycin-injured alveolospheres
| PRJNA824015 | ENA
Project description:Nine major cell populations among 46,716 cells were identified in mouse intestinal ischemia‒reperfusion (II/R) injury by single-cell RNA sequencing. For enterocyte cells, 11 subclusters were found, in which enterocyte cluster 1 (EC1), enterocyte cluster 3 (EC3), and enterocyte cluster 8 (EC8) were newly discovered cells in ischemia 45 min/reperfusion 720 min (I 45 min/R 720 min) group. EC1 and EC3 played roles in digestion and absorption, and EC8 played a role in cell junctions. For TA cells, after ischemia 45 min/reperfusion 90 min (I 45 min/R 90 min), many TA cells at the stage of proliferation were identified. For Paneth cells, Paneth cluster 3 was observed in the resting state of normal jejunum. After I 45 min/R 90 min, three new subsets were found, in which Paneth cluster 1 had good antigen presentation activity. The main functions of goblet cells were to synthesize and secrete mucus, and a novel subcluster (goblet cluster 5) with highly proliferative ability was discovered in I 45 min/R 90 min group. As a major part of immune system, the changes in T cells with important roles were clarified. Notably, enterocyte cells secreted Guca2b to interact with Gucy2c receptor on the membranes of stem cells, TA cells, Paneth cells, and goblet cells to elicit intercellular communication. One marker known as glutathione S-transferase mu 3 (GSTM3) affected intestinal mucosal barrier function by adjusting mitogen-activated protein kinases (MAPK) signaling during II/R injury. The data on the heterogeneity of intestinal cells, cellular communication and the mechanism of GSTM3 provide a cellular basis for treating II/R injury.
| S-EPMC10422115 | biostudies-literature
Project description:To determine the transcriptional programs initiated by IFN-λ to delay tissue restitution, we isolated intestinal crypts from the small intestine of VilCREIfnlr1fl/fl mice or WT littermates that have been irradiated and performed targeted transcriptomics analysis
2024-04-01 | GSE247149 | GEO
Project description:Renal recovery following injury relies on cellular regeneration. In the mouse kidney following injury, injured epithelial cells undergoes de-differentiate, proliferate and re-differentiate into functional cells, following a a tightly controlled genetic programme where specific sets of genes are up-regulated. We used microarrays to detail the global programme of gene expression underlying cellular regeneration following injury with or without a HDAC inhibitor, m4PTB, treatment and identified distinct classes of up-regulated genes during this process. Male BALB/c mice underwent 26 minute unilateral ischemia-reperfusion (IR) with contralateral nephrectomy treated with vehicle or 100 mg/kg m4PTB 24 h after inducing renal injury, and kidneys harvested for RNA extraction 12 h later. We sought to obtain kidneys within a similar degree of injury in order to carefully evaluate the effect of m4PTB on expression profiles. To that end, we selected kidneys according to three different criteria of injury: (1) level of serum creatinine at Day1, (2) the level of blood urea nitrogen (BUN) (3) Kim1 expression by qPCR at Day1.5 using haevested kidneys
2013-03-01 | E-GEOD-42247 | biostudies-arrayexpress