The Journal of nutrition · 2025
An Integrated Single-Cell Atlas of the Mouse Ileum Links Nutrient Metabolism with Epithelial and Immune Crosstalk.
СтатьяПоддержка исследования: вне правительства СШАПоддержка правительства СШАПоддержка NIH: внешняя программаНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Tang Yashu, Lu Peiran, Chowanadisai Winyoo, Smith Brenda J, Salak-Johnson Janeen L, Lucas Edralin A, Clarke Stephen L, Conway Tyrrell, Tang Minghua, Lin Dingbo
Аннотация
BACKGROUND: The ileum integrates nutrient absorption with mucosal immunity, yet its cell-type-specific functions remain poorly defined. Disruption of epithelial or immune pathways contributes to nutrient deficiency, Crohn's disease, and impaired barrier integrity. Single-cell RNA sequencing (scRNA-seq) provides the resolution needed to uncover epithelial differentiation and immune crosstalk that bulk approaches cannot resolve.
OBJECTIVES: This study aimed to map ileal cellular heterogeneity and define epithelial differentiation, nutrient metabolism programs, and epithelial-immune interactions relevant to health and disease.
METHODS: scRNA-seq was performed on ileal cells from 8-wk-old male C57BL/6J mice. Gene expression and clustering were analyzed using Seurat, with pseudotime trajectory, cell-cell communication, and pathway enrichment analyses applied to characterize intestinal dynamics.
RESULTS: A total of 32,076 ileal cells were identified, including 6 epithelial types and multiple immune populations. Enterocyte subclusters showed distinct nutrient-related functions: Ent_C1, C4, C7, and C8 were enriched for vitamin A absorption; Ent_C0, C1, C2 and C7 for carotenoid metabolism; and Ent_C1, C4, C7, C8, and C9 for vitamin B12 absorption. Coexpression of β-carotene oxygenase 2 (Bco2) and IL 18 (Il18) occurred across enterocytes, stem cells, and goblet cells, whereas noncanonical goblet cells exhibited high Bco2-Il18 expression together with signatures of fatty acid metabolism and stress responses. Plasmacytoid dendritic cells were identified as central regulators of immune-epithelial interactions.
CONCLUSIONS: This study provides the first integrated single-cell atlas of the mouse ileum, profiling both epithelial and immune cells and revealing nutrient metabolism programs and epithelial-immune crosstalk relevant to intestinal health and disease.
OBJECTIVES: This study aimed to map ileal cellular heterogeneity and define epithelial differentiation, nutrient metabolism programs, and epithelial-immune interactions relevant to health and disease.
METHODS: scRNA-seq was performed on ileal cells from 8-wk-old male C57BL/6J mice. Gene expression and clustering were analyzed using Seurat, with pseudotime trajectory, cell-cell communication, and pathway enrichment analyses applied to characterize intestinal dynamics.
RESULTS: A total of 32,076 ileal cells were identified, including 6 epithelial types and multiple immune populations. Enterocyte subclusters showed distinct nutrient-related functions: Ent_C1, C4, C7, and C8 were enriched for vitamin A absorption; Ent_C0, C1, C2 and C7 for carotenoid metabolism; and Ent_C1, C4, C7, C8, and C9 for vitamin B12 absorption. Coexpression of β-carotene oxygenase 2 (Bco2) and IL 18 (Il18) occurred across enterocytes, stem cells, and goblet cells, whereas noncanonical goblet cells exhibited high Bco2-Il18 expression together with signatures of fatty acid metabolism and stress responses. Plasmacytoid dendritic cells were identified as central regulators of immune-epithelial interactions.
CONCLUSIONS: This study provides the first integrated single-cell atlas of the mouse ileum, profiling both epithelial and immune cells and revealing nutrient metabolism programs and epithelial-immune crosstalk relevant to intestinal health and disease.