The Lgr5 receptor is a marker of intestinal stem cells (ISC s) that regulates Wnt/b‐catenin signaling. In this study, phenotype analysis of knockin/knockout Lgr5‐eGFP ‐IRES ‐Cre and Lgr5‐DTR eGFP embryos reveals that Lgr5 deficiency during Wnt‐mediated cytodifferentiation results in amplification of ISC s and early differentiation into Paneth cells, which can be counteracted by in utero treatment with the Wnt inhibitor LGK 974. Conditional ablation of Lgr5 postnatally, but not in adults, alters stem cell fate toward the Paneth lineage. Together, these in vivo studies suggest that Lgr5 is part of a feedback loop to adjust the Wnt tone in ISC s. Moreover, transcriptome analyses reveal that Lgr5 controls fetal ISC maturation associated with acquisition of a definitive stable epithelial phenotype, as well as the capacity of ISC s to generate their own extracellular matrix. Finally, using the ex vivo culture system, evidences are provided that Lgr5 antagonizes the Rspondin 2‐Wnt‐mediated response in ISC s in organoids, revealing a sophisticated regulatory process for Wnt signaling in ISC s.

中文翻译：

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LGR5通过发育中的肠中的干细胞控制细胞外基质的产生。

Lgr5受体是调节Wnt / b-catenin信号传导的肠道干细胞（ISC s）的标志物。在这项研究中，对敲入/敲除的Lgr5‐eGFP‐IRES‐Cre和Lgr5‐DTR eGFP胚胎的表型分析表明，Wnt介导的细胞分化过程中Lgr5缺乏会导致ISC扩增和早期分化为Paneth细胞，这可以通过抵消用Wnt抑制剂LGK 974进行宫内治疗。产后Lgr5的条件性消融（而不是成人）有条件地消融，改变了Paneth血统的干细胞命运。一起，这些体内研究表明，Lgr5是调节ISC中Wnt音调的反馈回路的一部分。此外，转录组分析显示Lgr5控制与确定的稳定上皮表型的获得相关的胎儿ISC成熟，以及ISC产生其自身细胞外基质的能力。最后，使用离体培养系统，提供证据表明Lgr5拮抗类器官中ISC中Rspondin 2-Wnt介导的应答，从而揭示了ISC中Wnt信号传导的复杂调控过程。