College of Animal Science, Zhejiang University, The Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Hangzhou, 310000, China.
Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, 310000, Zhejiang, China.
BMC Biol. 2022 May 30;20(1):123. doi: 10.1186/s12915-022-01321-3.
In mammals, transitioning from sole milk uptake to the intake of solid feed results in dramatic developmental changes in intestinal function and immunological status. In fact, weaning stress is often accompanied by intestinal inflammatory processes. To develop effective intervention strategies, it is necessary to characterize the developmental pattern and immune response that occurs on weaning, as we have done in this study for piglets.
To comprehensively delineate cell heterogeneity in ileum tissues and the underlying mechanisms in weaning-induced intestinal inflammation of piglets, we have analyzed the transcriptomes of 42,149 cells from ileum mucosa of normally suckling and post-weaned piglets. There were 31 cell subtypes including epithelial, stromal, and immune cells. A bifurcating trajectory was inferred to separate secretory and absorptive lineages. Integrated cross-species datasets showed well-conserved cellular architectures and transcription signatures between human and pig. Comparative analyses of cellular components, cell-cell communications, and molecular states revealed that T cell subpopulations were significantly altered in weaned piglets. We found that T helper (Th) 17 functional plasticity across changes in the cytokine milieu and the enrichment of granzyme B (GZMB)-expressing cytotoxic T cells potentially exacerbate mucosal inflammation via mitochondrial dysfunction in epithelial cells.
Our work has elucidated the single-cell molecular characteristics of the piglet ileum before and after weaning. We have provided an atlas that portrays the landscape of the intestinal pathophysiological inflammatory process associated with weaning, finding a level of conservation between human and pig that support the use of piglets as a model for human infants.
在哺乳动物中，从单纯摄入母乳过渡到固体饲料会导致肠道功能和免疫状态发生显著的发育变化。事实上，断奶应激通常伴随着肠道炎症过程。为了开发有效的干预策略，有必要对断奶时发生的发育模式和免疫反应进行特征描述，我们在这项针对仔猪的研究中就做到了这一点。
为了全面描绘正常哺乳和断奶后仔猪回肠组织中的细胞异质性和断奶诱导的肠道炎症的潜在机制，我们分析了来自正常哺乳和断奶后仔猪回肠黏膜的 42149 个细胞的转录组。其中包括上皮细胞、基质细胞和免疫细胞在内的 31 种细胞亚型。推断出一个分叉轨迹来分离分泌和吸收谱系。整合跨物种数据集显示，人类和猪之间存在着良好的细胞结构和转录特征保守性。细胞成分、细胞间通讯和分子状态的比较分析表明，断奶仔猪的 T 细胞亚群发生了显著变化。我们发现，Th17 功能的可塑性与细胞因子微环境的变化以及表达颗粒酶 B（GZMB）的细胞毒性 T 细胞的富集有关，这可能通过上皮细胞中线粒体功能障碍加剧黏膜炎症。
我们的工作阐明了仔猪断奶前后回肠的单细胞分子特征。我们提供了一个图谱，描绘了与断奶相关的肠道病理生理炎症过程的景观，发现了人类和猪之间的一定程度的保守性，支持将仔猪用作人类婴儿模型。
