美国斯坦福大学Michael Snyder等研究人员合作以单细胞分辨率观察人类肠道的组织结构。2023年7月19日，国际知名学术期刊《自然》发表了这一成果。

研究人员表示，肠道是一个复杂的器官，它促进消化、汲取营养、参与免疫监视、维持与微生物群的重要共生关系并影响整体健康。肠道长度超过九米，沿线的结构和功能存在差异。单个细胞类型的定位、细胞类型的发育轨迹和详细的细胞转录程序可能是这些功能差异的驱动因素。

为了更好地了解这些差异，研究人员使用多路复用成像和单核RNA及开放染色质检测法评估了来自九名供体的八个不同肠道部位的单细胞组织。通过系统分析，研究人员发现肠道不同区域的细胞组成存在很大差异，并展示了上皮亚型的复杂性，同时发现相同类型的细胞被组织成不同的邻近区和群落，从而突显了肠道中存在的不同免疫学微环境。研究人员还绘制了这些细胞的基因调控差异图，这些差异表明存在调控分化级联，并将肠道疾病遗传性与特定细胞类型联系起来。这些结果描述了该器官细胞组成、调控和组织的复杂性，是了解人类生物学和疾病的重要参考图谱。

附：英文原文

Title: Organization of the human intestine at single-cell resolution

Author: Hickey, John W., Becker, Winston R., Nevins, Stephanie A., Horning, Aaron, Perez, Almudena Espin, Zhu, Chenchen, Zhu, Bokai, Wei, Bei, Chiu, Roxanne, Chen, Derek C., Cotter, Daniel L., Esplin, Edward D., Weimer, Annika K., Caraccio, Chiara, Venkataraaman, Vishal, Schrch, Christian M., Black, Sarah, Brbi, Maria, Cao, Kaidi, Chen, Shuxiao, Zhang, Weiruo, Monte, Emma, Zhang, Nancy R., Ma, Zongming, Leskovec, Jure, Zhang, Zhengyan, Lin, Shin, Longacre, Teri, Plevritis, Sylvia K., Lin, Yiing, Nolan, Garry P., Greenleaf, William J., Snyder, Michael

Issue&Volume: 2023-07-19

Abstract: The intestine is a complex organ that promotes digestion, extracts nutrients, participates in immune surveillance, maintains critical symbiotic relationships with microbiota and affects overall health1. The intesting has a length of over nine metres, along which there are differences in structure and function2. The localization of individual cell types, cell type development trajectories and detailed cell transcriptional programs probably drive these differences in function. Here, to better understand these differences, we evaluated the organization of single cells using multiplexed imaging and single-nucleus RNA and open chromatin assays across eight different intestinal sites from nine donors. Through systematic analyses, we find cell compositions that differ substantially across regions of the intestine and demonstrate the complexity of epithelial subtypes, and find that the same cell types are organized into distinct neighbourhoods and communities, highlighting distinct immunological niches that are present in the intestine. We also map gene regulatory differences in these cells that are suggestive of a regulatory differentiation cascade, and associate intestinal disease heritability with specific cell types. These results describe the complexity of the cell composition, regulation and organization for this organ, and serve as an important reference map for understanding human biology and disease.

DOI: 10.1038/s41586-023-05915-x

Source: https://www.nature.com/articles/s41586-023-05915-x