ArticleCellular and molecular gastroenterology and hepatology2019
Single-Cell Analysis Reveals Regional Reprogramming During Adaptation to Massive Small Bowel Resection in Mice.
Article in Cellular and molecular gastroenterology and hepatology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed.
- Biological Insights into Intestinal Adaptation from Preclinical Models of Short Bowel Syndrome.Cells · 2026Review
- Alterations in biopterin metabolism and the effects of tetrahydrobiopterin supplementation in a rat model of short bowel syndrome.Pediatric surgery international · 2026Article
- SMURF: soft-segmentation for single-cell reconstruction and topological analysis of spatial transcriptomic data.Nature communications · 2026Article
- A Gut-Restricted Liver X Receptor Agonist Ameliorates Liver Injury in Experimental Short Bowel Syndrome.Gastroenterology · 2026Article
- VRAC coordinates the trade-off between nutrient absorption and antimicrobial defense in enterocytes against inflammation.Nature communications · 2026Article
- Molecular Mechanisms of Intestinal Adaptation in Short Bowel Syndrome: A Comprehensive Review.International journal of molecular sciences · 2026Review
- Cellular senescence in human liver under normal aging and cancer.Cell genomics · 2026Article
- Enteral Feeding With Omega-3 Polyunsaturated Fatty Acids Mitigates Liver Injury Following Massive Intestinal Resection.Cellular and molecular gastroenterology and hepatology · 2026Article
- Xenotransplanted human organoids identify transepithelial zinc transport as a key mediator of intestinal adaptation.Nature communications · 2024Article
- Enteroendocrine Reprogramming by Altered Epithelial-Mesenchymal Crosstalk in Metabolic Surgery.Journal of metabolic and bariatric surgery · 2024Review
- Epithelial zonation along the mouse and human small intestine defines five discrete metabolic domains.Nature cell biology · 2024Article
- Article
- Disruption of Enterohepatic Circulation of Bile Acids Ameliorates Small Bowel Resection Associated Hepatic Injury.Journal of pediatric surgery · 2023Article
- Intestinal Knockout of Peroxisome Proliferator-Activated Receptor-Alpha Affects Structural Adaptation but not Liver Injury Following Massive Enterectomy.Journal of pediatric surgery · 2023Article
- An Overview of Short-Bowel Syndrome in Pediatric Patients: Focus on Clinical Management and Prevention of Complications.Nutrients · 2023Review
- In vitro cancer models as an approach to identify targetable developmental phenotypes in cancer stem cells.In vitro models · 2023Article
- Intestinal epithelial c-Maf expression determines enterocyte differentiation and nutrient uptake in mice.The Journal of experimental medicine · 2022Article
- Intestinal cellular heterogeneity and disease development revealed by single-cell technology.Cell regeneration (London, England) · 2022Review
- Lipid absorption and overall intestinal lymphatic transport are impaired following partial small bowel resection in mice.Scientific reports · 2022Article
- Distal Small Bowel Resection Yields Enhanced Intestinal and Colonic Adaptation.The Journal of surgical research · 2022Article
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Authors and funding
11 authors.
Funding
Abstract
BACKGROUND &
aimsThe small intestine (SI) displays regionality in nutrient and immunological function. Following SI tissue loss (as occurs in short gut syndrome, or SGS), remaining SI must compensate, or "adapt"; the capacity of SI epithelium to reprogram its regional identity has not been described. Here, we apply single-cell resolution analyses to characterize molecular changes underpinning adaptation to SGS.
methodsSingle-cell RNA sequencing was performed on epithelial cells isolated from distal SI of mice following 50% proximal small bowel resection (SBR) vs sham surgery. Single-cell profiles were clustered based on transcriptional similarity, reconstructing differentiation events from intestinal stem cells (ISCs) through to mature enterocytes. An unsupervised computational approach to score cell identity was used to quantify changes in regional (proximal vs distal) SI identity, validated using immunofluorescence, immunohistochemistry, qPCR, western blotting, and RNA-FISH.
resultsUniform Manifold Approximation and Projection-based clustering and visualization revealed differentiation trajectories from ISCs to mature enterocytes in sham and SBR. Cell identity scoring demonstrated segregation of enterocytes by regional SI identity: SBR enterocytes assumed more mature proximal identities. This was associated with significant upregulation of lipid metabolism and oxidative stress gene expression, which was validated via orthogonal analyses. Observed upstream transcriptional changes suggest retinoid metabolism and proximal transcription factor Creb3l3 drive proximalization of cell identity in response to SBR.
conclusionsAdaptation to proximal SBR involves regional reprogramming of ileal enterocytes toward a proximal identity. Interventions bolstering the endogenous reprogramming capacity of SI enterocytes-conceivably by engaging the retinoid metabolism pathway-merit further investigation, as they may increase enteral feeding tolerance, and obviate intestinal failure, in SGS.
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