Department of Molecular Cell Biology, Weizmann Institute of Science, 7610001, Rehovot, Israel.
Program in Craniofacial Biology and Department of Orofacial Sciences, University of California, San Francisco, CA, 94110, USA.
Nat Commun. 2020 Apr 22;11(1):1936. doi: 10.1038/s41467-020-15714-x.
The intestinal epithelium is a structured organ composed of crypts harboring Lgr5+ stem cells, and villi harboring differentiated cells. Spatial transcriptomics have demonstrated profound zonation of epithelial gene expression along the villus axis, but the mechanisms shaping this spatial variability are unknown. Here, we combine laser capture micro-dissection and single cell RNA sequencing to uncover spatially zonated populations of mesenchymal cells along the crypt-villus axis. These include villus tip telocytes (VTTs) that express Lgr5, a gene previously considered a specific crypt epithelial stem cell marker. VTTs are elongated cells that line the villus tip epithelium and signal through Bmp morphogens and the non-canonical Wnt5a ligand. Their ablation is associated with perturbed zonation of enterocyte genes induced at the villus tip. Our study provides a spatially-resolved cell atlas of the small intestinal stroma and exposes Lgr5+ villus tip telocytes as regulators of the epithelial spatial expression programs along the villus axis.
肠上皮是一个结构组织器官，由含有 Lgr5+干细胞的隐窝和含有分化细胞的绒毛组成。空间转录组学已经证明了上皮基因表达沿着绒毛轴的深刻分区，但形成这种空间变异性的机制尚不清楚。在这里，我们结合激光捕获显微切割和单细胞 RNA 测序，揭示了沿着隐窝-绒毛轴的间质细胞的空间分区群体。这些包括表达 Lgr5 的绒毛尖端 telocytes（VTTs），Lgr5 是以前被认为是特定隐窝上皮干细胞标记的基因。VTTs 是排列在绒毛尖端上皮的细长细胞，通过 Bmp 形态发生素和非经典 Wnt5a 配体发出信号。它们的消融与绒毛尖端诱导的肠细胞基因分区紊乱有关。我们的研究提供了小肠基质的空间分辨细胞图谱，并揭示了 Lgr5+绒毛尖端 telocytes 作为沿着绒毛轴上皮空间表达程序的调节剂。
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