A Roadmap for the Human Gut Cell Atlas

Nature Reviews Gastroenterology & Hepatology, Год журнала: 2023, Номер 20(9), С. 597 - 614

Опубликована: Май 31, 2023

Язык: Английский

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A spatial expression atlas of the adult human proximal small intestine

Nature, Год журнала: 2024, Номер 632(8027), С. 1101 - 1109

Опубликована: Авг. 7, 2024

Язык: Английский

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Single-cell atlas of the small intestine throughout the human lifespan demonstrates unique features of fetal immune cells

Mucosal Immunology, Год журнала: 2024, Номер 17(4), С. 599 - 617

Опубликована: Март 28, 2024

Язык: Английский

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Piezo1 promotes the progression of necrotizing enterocolitis by activating the Ca2(+)/CaMKII-dependent pathway

Communications Biology, Год журнала: 2025, Номер 8(1)

Опубликована: Март 12, 2025

Necrotizing enterocolitis (NEC) is a devastating inflammatory bowel necrosis of preterm infants with limited therapeutic approaches. Mounting evidence supports the role Piezo1, namely, widely distributed mechanosensor in intestinal epithelial cells (IECs), inflammation but its underlying mechanism development NEC remains unexplored. In this study, we demonstrated that Piezo1 expression was higher lower gestational age. C57BL/6J mice wherein deleted IECs (villin-specific knockout mice; Piezo1flox/floxVillinCre+) and Piezo1flox/flox littermates were subjected to induce NEC, regulated barrier function, restricted cytokines secretion, diminished response mouse models. elevated cytosolic Ca2+ levels activated Ca2+/calmodulin-dependent protein kinase II (CaMKII) promote CaMKII/NF-κB interaction NF-κB activation vitro. Finally, effects CaMKII inhibitor, KN93, evaluated both vitro vivo models, functions suppressed partially by KN93. characterise undefined which may be attributed differential calcium under pathophysiological conditions. Intestinal regulates secretion necrotizing enterocolitis.

Язык: Английский

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Identification and Exploration of Pyroptosis-Related Genes in Macrophage Cells Reveal Necrotizing Enterocolitis Heterogeneity Through Single-Cell and Bulk-Sequencing

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(9), С. 4036 - 4036

Опубликована: Апрель 24, 2025

Necrotizing enterocolitis (NEC) is an acute intestine dysfunction intestinal disorder characterized by inflammation and cell death, including pyroptosis. Previous studies have implicated pyroptosis, particularly via NLRP3 inflammatory activation, contribute to the development of NEC. However, genetic molecular mechanisms underlying pyroptosis in NEC pathogenesis sequelae remain unclear. Our study aimed identify pyroptosis-related populations genes explore potential therapeutic targets. Single-cell RNA sequencing (scRNA-seq) data were analyzed related Weighted gene correlation network analysis (WGCNA) bulk RNA-seq was performed modules associate with Cell–cell communication employed investigate intercellular signaling networks. Gene Set Enrichment Analysis (GSEA) conducted compare pathways enriched high low TREM1-expressing subgroups. Immunofluorescence staining detect TREM1+CD163+ macrophages intestines. PCR Western blot expression mRNA proteins tissues cells. scRNA-seq revealed increased macrophage abundance NEC, one cluster (cluster 4) exhibiting a markedly elevated score. WGCNA identified module (MEbrown) that positively correlated Five (TREM1, TLN1, NOTCH2, MPZL1, ADA) within this as diagnostic markers Furthermore, we novel subpopulation, TREM1+CD163+, suggested interact other cells primarily through NAMPT/ITGA5/ITGB1 CCL3/CCR1 pathways. GSEA significant association between TREM1 proliferation, inflammation. In vivo vitro experiments confirmed increase NEC-affected inhibition THP-1 significantly reduced pro-inflammatory cytokines proteins. We population plays crucial role during progression. findings elucidate biological functions TREM1, demonstrating its upregulation pro-pyroptosis effects vitro. These insights advance our understanding suggest target for

Язык: Английский

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Present and future of microbiome-targeting therapeutics

Journal of Clinical Investigation, Год журнала: 2025, Номер 135(11)

Опубликована: Июнь 1, 2025

A large body of evidence suggests that single- and multiple-strain probiotics synbiotics could have roles in the management specific gastrointestinal disorders. However, ongoing concerns regarding quality heterogeneity clinical data, safety vulnerable populations, lack regulation products containing live microbes are barriers to widespread use. Safety regulatory issues must be addressed new technologies considered. One alternative future strategy is use synthetic bacterial communities, defined as manually assembled consortia two or more bacteria originally derived from human tract. Synthetic communities can model functional, ecological, structural aspects native within tract, occupying varying nutritional niches providing host with a stable, robust, diverse gut microbiota prevent pathobiont colonization by way resistance. Alternatively, phage therapy lytic treat infections. The rise antimicrobial resistance has led renewed interest therapy, high specificity phages for their hosts spurred using phage-based approaches precisely modulate microbiome. In this Review, we consider present microbiome-targeting therapies, special focus on early-life applications, such prevention necrotizing enterocolitis.

Язык: Английский

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Selenium deficiency is functionally linked with the molecular etiopathogenesis of necrotizing enterocolitis (NEC)

Functional & Integrative Genomics, Год журнала: 2025, Номер 25(1)

Опубликована: Июнь 3, 2025

Abstract Necrotizing enterocolitis (NEC) is a severe and often catastrophic gastrointestinal emergency that predominantly affects neonates, especially those born prematurely, associated with high rates of morbidity mortality. Despite its significant clinical impact, the precise etiology molecular pathogenesis NEC remain incompletely understood. In this study, we conducted global transcriptomic profiling using high-throughput RNA sequencing in 11 premature neonates diagnosed NEC, following rigorous inclusion exclusion criteria. Compared to healthy controls, identified 1,204 differentially expressed genes (DEGs), including 636 upregulated 568 downregulated transcripts. Notably, involved hypoxia-induced apoptosis (e.g., HIF1 AAS3 , AAS1 ), caspase cascade ( BCL2 BCL6 CASP5 CASP7 inflammation IL1RAP IL6ST TNFAIP3 TNFRSF10 A TLR6 TLR10 ) were significantly upregulated. contrast, IL18 key modulator inflammatory responses, was downregulated. Interestingly, several encoding selenoproteins GPX1 GPX4 SELENON SELENOM SELENOF SELENOW SELENOT also downregulated, suggesting evidence selenium deficiency. Gene ontology pathway enrichment analyses revealed widespread dysregulation pathways related hypoxia response, systemic inflammation, coagulation, antimicrobial defense, mitochondrial function, autophagy, metabolism, apoptosis. Collectively, our findings provide novel insights into underpinnings infants suggest hypoxia, oxidative stress, deficiency, programmed cell death contribute pathogenesis.

Язык: Английский

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More than nutrition: Therapeutic potential and mechanism of human milk oligosaccharides against necrotizing enterocolitis

Life Sciences, Год журнала: 2024, Номер 339, С. 122420 - 122420

Опубликована: Янв. 11, 2024

Язык: Английский

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Epigenetic Insights Into Necrotizing Enterocolitis: Unraveling Methylation-Regulated Biomarkers

Inflammation, Год журнала: 2024, Номер 48(1), С. 236 - 253

Опубликована: Май 30, 2024

Necrotizing enterocolitis (NEC) is a multifactorial gastrointestinal disease with high morbidity and mortality among premature infants. This study aimed to identify novel methylation-regulated biomarkers in NEC intestinal tissue through multiomics analysis. We analyzed DNA methylation transcriptome datasets from ileum colon tissues of patients NEC. methylation-related differential genes (MrDEGs) based on the rule that degree promoter region inversely proportional RNA transcription. These MrDEGs included ADAP1, GUCA2A, BCL2L14, FUT3, MISP, USH1C, ITGA3, UNC93A IL22RA1. Single-cell data revealed were mainly located epithelial part tissue. verified Target gene bisulfite sequencing RT-qPCR. successfully identified IL22RA1 primarily expressed villus cells single-cell data. Through single-gene set enrichment analysis, we found these participate pathological process T-cell differentiation suppression inflammation enhances our understanding pathogenesis may promote development new precision medicine methods for prediction diagnosis.

Язык: Английский

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cellanneal: A user-friendly deconvolution software for transcriptomics data

The Journal of Open Source Software, Год журнала: 2024, Номер 9(93), С. 5610 - 5610

Опубликована: Янв. 12, 2024

Single-cell sequencing methods enable precise characterization of gene expression patterns in individual cells.However, they may provide inaccurate information about the cell type composition samples, as required preprocessing procedures such tissue dissociation or sorting affect viability different types to varying extent (Erdmann-Pham et al., 2021).Further, especially clinical context, single-cell patient samples is currently not routinely applied because high cost and expertise, while bulk more prevalent.

Язык: Английский

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