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单细胞转录组分析揭示了人类肠道中不同的营养吸收功能。

Single-cell transcriptome analysis reveals differential nutrient absorption functions in human intestine.

机构信息

The State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.

The MOE Key Laboratory of Bioinformatics, Center for Synthetic & Systems Biology, School of Life Sciences, Tsinghua University, Beijing, China.

出版信息

J Exp Med. 2020 Feb 3;217(2). doi: 10.1084/jem.20191130.

Abstract

The intestine plays an important role in nutrient digestion and absorption, microbe defense, and hormone secretion. Although major cell types have been identified in the mouse intestinal epithelium, cell type-specific markers and functional assignments are largely unavailable for human intestine. Here, our single-cell RNA-seq analyses of 14,537 epithelial cells from human ileum, colon, and rectum reveal different nutrient absorption preferences in the small and large intestine, suggest the existence of Paneth-like cells in the large intestine, and identify potential new marker genes for human transient-amplifying cells and goblet cells. We have validated some of these insights by quantitative PCR, immunofluorescence, and functional analyses. Furthermore, we show both common and differential features of the cellular landscapes between the human and mouse ilea. Therefore, our data provide the basis for detailed characterization of human intestine cell constitution and functions, which would be helpful for a better understanding of human intestine disorders, such as inflammatory bowel disease and intestinal tumorigenesis.

摘要

肠道在营养消化和吸收、微生物防御和激素分泌方面发挥着重要作用。尽管在小鼠肠道上皮中已经确定了主要的细胞类型,但人类肠道的细胞类型特异性标记物和功能分配在很大程度上仍然未知。在这里,我们对来自人回肠、结肠和直肠的 14537 个上皮细胞进行了单细胞 RNA-seq 分析,揭示了小肠和大肠在营养吸收方面的不同偏好,提示大肠中存在类似于 Paneth 细胞的细胞,并且鉴定出了人瞬态扩增细胞和杯状细胞的潜在新标记基因。我们通过定量 PCR、免疫荧光和功能分析验证了其中的一些见解。此外,我们还展示了人回肠和小鼠回肠之间细胞景观的共同和差异特征。因此,我们的数据为详细描述人类肠道细胞组成和功能提供了基础,这将有助于更好地理解人类肠道疾病,如炎症性肠病和肠道肿瘤发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60c9/7041720/656a64ed5d5f/JEM_20191130_Fig4.jpg

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