The State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
The State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China; Guangzhou Laboratory, Guangzhou, China.
Cell Rep. 2022 Jul 12;40(2):111053. doi: 10.1016/j.celrep.2022.111053.
After gut tube patterning in early embryos, the cellular and molecular changes of developing stomach and intestine remain largely unknown. Here, combining single-cell RNA sequencing and spatial RNA sequencing, we construct a spatiotemporal transcriptomic landscape of the mouse stomach and intestine during embryonic days E9.5-E15.5. Several subpopulations are identified, including Lox stomach mesenchyme, Aldh1a3 small-intestinal mesenchyme, and Adamdec1 large-intestinal mesenchyme. The regionalization and heterogeneity of both the epithelium and the mesenchyme can be traced back to E9.5. The spatiotemporal distributions of cell clusters and the mesenchymal-epithelial interaction analysis indicate that a coordinated development of the epithelium and mesenchyme contribute to the stomach regionalization, intestine segmentation, and villus formation. Using the gut tube-derived organoids, we find that the cell fate of the foregut and hindgut can be switched by the regional niche factors, including fibroblast growth factors (FGFs) and retinoic acid (RA). This work lays a foundation for further dissection of the mechanisms governing this process.
在早期胚胎的肠道模式形成之后，发育中的胃和肠的细胞和分子变化在很大程度上仍然未知。在这里，我们结合单细胞 RNA 测序和空间 RNA 测序，构建了胚胎期 E9.5-E15.5 期间小鼠胃和肠的时空转录组图谱。鉴定出了几个亚群，包括 Lox 胃间充质、Aldh1a3 小肠间充质和 Adamdec1 大肠间充质。上皮和间充质的区域化和异质性可以追溯到 E9.5。细胞簇的时空分布和间质-上皮相互作用分析表明，上皮和间充质的协调发育有助于胃的区域化、肠的分段和绒毛的形成。使用肠道管源性类器官，我们发现前肠和后肠的细胞命运可以通过区域龛位因子（包括成纤维细胞生长因子 (FGFs) 和视黄酸 (RA)）来切换。这项工作为进一步解析控制这一过程的机制奠定了基础。
