Department of Molecular Life Sciences, University of Zurich, Switzerland.
Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic.
PLoS Biol. 2020 Dec 11;18(12):e3001032. doi: 10.1371/journal.pbio.3001032. eCollection 2020 Dec.
Despite recent progress in recognizing the importance of mesenchymal cells for the homeostasis of the intestinal system, the current picture of how these cells communicate with the associated epithelial layer remains unclear. To describe the relevant cell populations in an unbiased manner, we carried out a single-cell transcriptome analysis of the adult murine colon, producing a high-quality atlas of matched colonic epithelium and mesenchyme. We identify two crypt-associated colonic fibroblast populations that are demarcated by different strengths of platelet-derived growth factor receptor A (Pdgfra) expression. Crypt-bottom fibroblasts (CBFs), close to the intestinal stem cells, express low levels of Pdgfra and secrete canonical Wnt ligands, Wnt potentiators, and bone morphogenetic protein (Bmp) inhibitors. Crypt-top fibroblasts (CTFs) exhibit high Pdgfra levels and secrete noncanonical Wnts and Bmp ligands. While the Pdgfralow cells maintain intestinal stem cell proliferation, the Pdgfrahigh cells induce differentiation of the epithelial cells. Our findings enhance our understanding of the crosstalk between various colonic epithelial cells and their associated mesenchymal signaling hubs along the crypt axis-placing differential Pdgfra expression levels in the spotlight of intestinal fibroblast identity.
尽管最近在认识间质细胞对于肠道系统稳态的重要性方面取得了进展，但这些细胞与相关上皮层如何相互交流的当前情况仍不清楚。为了以无偏倚的方式描述相关细胞群体，我们对成年小鼠结肠进行了单细胞转录组分析，生成了高质量的匹配结肠上皮和间充质图谱。我们确定了两个与隐窝相关的结肠成纤维细胞群体，它们由血小板衍生生长因子受体 A（Pdgfra）表达的不同强度来区分。靠近肠干细胞的隐窝底部成纤维细胞（CBFs）表达低水平的 Pdgfra，并分泌经典 Wnt 配体、Wnt 增强子和骨形态发生蛋白（Bmp）抑制剂。隐窝顶部成纤维细胞（CTFs）则表达高水平的 Pdgfra，并分泌非经典 Wnt 和 Bmp 配体。虽然低水平 Pdgfra 的细胞维持肠干细胞的增殖，但高水平 Pdgfra 的细胞诱导上皮细胞的分化。我们的发现增强了我们对各种结肠上皮细胞与其沿隐窝轴的相关间充质信号枢纽之间相互作用的理解——将差异 Pdgfra 表达水平置于肠道成纤维细胞身份的聚光灯下。
