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Single-Cell Transcriptome and Microbiome Profiling Uncover Ileal Immune Impairment in Intrauterine Growth-Retarded Piglets

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机构: [1]Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation, College of Life Sciences, Hunan Normal University, Changsha, China. [2]Institute of Subtropical Agriculture, the Chinese Academy of Sciences, Changsha, China. [3]Xuanwu Hospital, Capital Medical University, Beijing 100053, China. [4]College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, China. [5]College of Animal Science and Technology, Hunan Agricultural University, Changsha, China. [6]Hunan Provincial Key Laboratory of the Traditional Chinese Medicine Agricultural Biogenomics, Changsha Medical University, Changsha, China.
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关键词: Intrauterine growth retardation intestine immune cell single-cell RNA sequencing gut microbiota

摘要:
Impaired intestinal immune function is commonly observed in neonates with intrauterine growth retardation (IUGR), yet its underlying mechanisms and regulatory pathways remain poorly understood. Therefore, we aimed to investigate gene regulatory patterns and microbiota alterations in IUGR piglets.Three newborn IUGR piglets and three normal littermates were selected from the same sow and sacrificed at seven days of age. Ileal digesta was collected for 16S rRNA amplicon sequencing (16S-seq), and ileum segments were dissociated for single-cell RNA sequencing (scRNA-seq).The scRNA-seq results revealed a reduced proportion of plasma B cells in IUGR piglets, along with alterations in the distribution of various T cell subsets. KEGG pathway analysis further indicated a downregulation of the B cell receptor signaling pathway in B cells from IUGR piglets. In contrast, both the T cell receptor signaling pathway and antigen processing and presentation were attenuated in T cells. Pseudotime trajectory analysis suggested that the differentiation of B cells was impaired in IUGR piglets. SCENIC analysis revealed that GATA3, IRF2, and BCL11A were downregulated in T cells of IUGR piglets. The 16S-seq results revealed that α-diversity was lower in IUGR piglets. At the genus level, the relative abundance of Prevotella was significantly lower in IUGR piglets.Significant changes were identified in the proportions of B and T cells, their associated signaling pathways, and intestinal microbiota composition in IUGR piglets, suggesting underlying immune dysfunction and dysbiosis.We identified novel immune-related transcription factors and key microbes as potential therapeutic targets, shedding light on strategies for preventing and treating IUGR.Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.

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出版当年[2025]版
大类 | 4 区 医学
小类 | 4 区 药学
最新[2025]版
大类 | 4 区 医学
小类 | 4 区 药学
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第一作者机构: [1]Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation, College of Life Sciences, Hunan Normal University, Changsha, China. [2]Institute of Subtropical Agriculture, the Chinese Academy of Sciences, Changsha, China.
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通讯机构: [2]Institute of Subtropical Agriculture, the Chinese Academy of Sciences, Changsha, China. [6]Hunan Provincial Key Laboratory of the Traditional Chinese Medicine Agricultural Biogenomics, Changsha Medical University, Changsha, China.
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