Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
Nat Metab. 2023 Nov;5(11):1858-1869. doi: 10.1038/s42255-023-00905-9. Epub 2023 Oct 19.
The intestinal epithelium is replaced every few days. Enterocytes are shed into the gut lumen predominantly from the tips of villi and have been believed to rapidly die upon their dissociation from the tissue. However, technical limitations prohibited studying the cellular states and fates of shed intestinal cells. Here we show that shed epithelial cells remain viable and upregulate distinct anti-microbial programmes upon shedding, using bulk and single-cell RNA sequencing of male mouse intestinal faecal washes. We further identify abundant shedding of immune cells, which is elevated in mice with dextran sulfate sodium-induced colitis. We find that faecal host transcriptomics reflect changes in the intestinal tissue following perturbations. Our study suggests potential functions of shed cells in the intestinal lumen and demonstrates that host cell transcriptomes in intestinal washes can be used to probe tissue states.
肠道上皮细胞每隔几天就会被替换。肠细胞主要从绒毛的顶端脱落到肠腔中，人们一直认为它们一旦与组织分离就会迅速死亡。然而，技术限制使得研究脱落的肠细胞的细胞状态和命运变得困难。在这里，我们通过对雄性小鼠肠道粪便冲洗物的单细胞和批量 RNA 测序，发现脱落的上皮细胞在脱落时仍然保持存活，并上调了独特的抗微生物程序。我们还进一步发现大量的免疫细胞脱落，在葡聚糖硫酸钠诱导的结肠炎小鼠中这种脱落更为明显。我们发现粪便中的宿主转录组学反映了肠道组织在受到干扰后的变化。我们的研究表明脱落细胞在肠道腔中可能具有潜在的功能，并证明了肠道冲洗物中的宿主转录组可以用于探测组织状态。
