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约束克罗恩病单细胞RNA测序揭示纤维细胞异质性和细胞间相互作用

Pranab K Mukherjee¹, Quang Tam Nguyen¹, Jiannan Li²

¹Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio; Center for Global Translational Inflammatory Bowel Disease Research, Cleveland Clinic, Cleveland, Ohio.

Gastroenterology

|July 28, 2023

概括

这项研究揭示了使用单细胞RNA测序在克罗恩病狭窄的纤维细胞异质性. 卡德林-11 (CDH11) 被确定为治疗纤维性肠狭窄症的关键治疗标.

科学领域:

胃肠病学胃肠病学
免疫学免疫学免疫学
分子生物学分子生物学

背景情况:

克罗恩氏病 (CD) 的发病包括纤维细胞激活和细胞外基质沉积,导致肠道狭窄.
了解纤维细胞异质性和功能对于识别CD狭窄的新疗法目标至关重要.

研究的目的:

为了生成一个单细胞RNA测序 (scRNAseq) 的纤维细胞图谱在严格的CD肠道.
在CD狭窄的纤维细胞异质性和细胞间通信的特征.
为了验证CD狭窄形成的潜在治疗点.

主要方法:

在99个来自13个CD切除和7个正常对照的组织样本上进行了scRNAseq,分析了409,001个细胞.
将样品分成粘膜/粘膜下部和肌肉自身以进行不同的分析.
使用分子和体内模型作为治疗点验证了cadherin-11 (CDH11).

主要成果:

在严格培养的CD中显示出显著的纤维细胞异质性,主要在粘膜/粘膜下.
确定了CXCL14+和MMP/WNT5A+纤维细胞作为CD收缩信号的关键参与者.
证明了CDH11的广泛表达和上调,证实了其益菌作用,并将其作为治疗点进行验证.

结论:

这项研究提供了CD狭窄的纤维细胞的全面scRNAseq地图,揭示了新的细胞相互作用.
卡德林-11 (CDH11) 已被验证为缓解克罗恩病狭窄性纤维化的有前途的治疗标.
本资源有助于理解CD狭窄病原体和开发新的治疗策略.

关键词:

克罗恩氏病是一种慢性病.一个单细胞的单细胞.严格的结构结构.治疗疗法治疗疗法

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