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结肠上皮细胞多样性在健康和炎症性肠病

Kaushal Parikh^1,2, Agne Antanaviciute^1,2,3, David Fawkner-Corbett^1,2,4

¹Medical Research Council (MRC) Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford, Oxford, UK.

|March 1, 2019

概括

研究人员发现了新的结肠上皮细胞亚型和一种新的pH感应细胞. 在炎症性肠病 (IBD) 中,杯状细胞变化和减少的WFDC2抗蛋白酶有助于屏障破坏.

科学领域:

胃肠病学
细胞生物学
免疫学

背景情况:

结肠上皮对于宿主微生物相互作用,粘膜免疫,营养循环和屏障功能至关重要.
表皮屏障的破坏是炎症性肠病 (IBD) 的标志,但具体细胞亚型的贡献仍然不清楚.

研究的目的:

从IBD患者和对照组中分析单个结肠上皮细胞,以了解细胞亚型在屏障完整性中的作用.
确定IBD表皮屏障功能障碍的新细胞亚型和分子机制.

主要方法:

来自IBD患者和健康对照者的结肠上皮细胞单细胞RNA测序.
识别和表征不同的上皮细胞亚型和转录状态.
在体内验证已识别的分子和细胞过程.

主要成果:

发现了以前未知的结肠上皮细胞亚型,包括密室内的原生细胞,结肠细胞和杯状细胞梯度.
鉴定了一种在炎症和癌症中失调的新型pH感应吸收细胞 (表达OTOP2和uroguanylin).
在IBD中观察到玻璃杯细胞的位置重塑,与抑制细菌生长和保持上皮屏障完整性的WFDC2抗蛋白酶的下调一致.

结论:

单细胞分析揭示了复杂的结肠上皮细胞异质性,并确定了新的细胞类型.
通过抑制细菌入侵和减少粘膜炎症,WFDC2在维持上皮屏障功能方面发挥着至关重要的作用.
特定的上皮细胞亚型和WFDC2等分子的失调是IBD障碍分解的基本决定因素.

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