在炎症性肠病中对人类结肠介质的结构重塑
James Kinchen1, Hannah H Chen1, Kaushal Parikh1
1MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK; Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK.
Cell
|October 2, 2018
概括
结肠介质细胞表现出令人惊的多样性,其中一个特定的子集支持上皮干细胞. 在大肠炎中,这些细胞变得失调,促进炎症和阻碍性肠病 (IBD) 的障碍功能.
科学领域:
- 胃肠病学
- 细胞生物学
- 免疫学
背景情况:
- 肠介质细胞对肠道健康至关重要,影响上皮质平衡,矩阵重塑,免疫力和炎症.
- 结肠介质细胞的异质性和特异性作用,特别是与上皮干细胞和炎症状况有关的作用,在很大程度上仍未被探索.
研究的目的:
- 通过单细胞分析来定义结肠介质中的细胞异质性.
- 识别参与维持结肠上皮干细胞功能的特定介质细胞子集.
- 研究结肠膜细胞在结肠炎和炎症性肠病 (IBD) 中的作用.
主要方法:
- 超过16500个结肠介质细胞的无偏向单细胞RNA测序.
- 转录分析以识别不同的纤维细胞子集,细胞周细胞和肌纤维细胞.
- 在体内研究以评估介质细胞群对表皮功能和大肠炎期间疾病严重性的影响.
主要成果:
- 在结肠介质中发现了四种不同的纤维细胞子集,细胞圈和肌纤维细胞.
- 发现表达SOX6,F3 (CD142) 和WNT基因的特定中细胞群对于结肠上皮干细胞功能至关重要.
- 大肠炎诱导了该位的失调,并促进了表达TNFSF14,IL-33和lysyl氧化酶的活化介质群体,从而损害了上皮细胞的增殖并加剧了疾病的严重程度.
结论:
- 结肠介质表现出显著的细胞异质性,不同的子集起着专门的作用.
- 一个表达SOX6-F3-WNT的介质细胞对于维持结肠上皮干细胞功能至关重要.
- 大肠炎期间中细胞的激活有助于IBD的炎症,屏障功能障碍和疾病严重程度.
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