Several cell populations have been reported to possess intestinal stem cell (ISC) activity during homeostasis and injury-induced regeneration. Here, we explored inter-relationships between putative mouse ISC populations by comparative RNA-sequencing (RNA-seq). The transcriptomes of multiple cycling ISC populations closely resembled Lgr5⁺ ISCs, the most well-defined ISC pool, but Bmi1-GFP⁺ cells were distinct and enriched for enteroendocrine (EE) markers, including Prox1. Prox1-GFP⁺ cells exhibited sustained clonogenic growth in vitro, and lineage-tracing of Prox1⁺ cells revealed long-lived clones during homeostasis and after radiation-induced injury in vivo. Single-cell mRNA-seq revealed two subsets of Prox1-GFP⁺ cells, one of which resembled mature EE cells while the other displayed low-level EE gene expression but co-expressed tuft cell markers, Lgr5 and Ascl2, reminiscent of label-retaining secretory progenitors. Our data suggest that the EE lineage, including mature EE cells, comprises a reservoir of homeostatic and injury-inducible ISCs, extending our understanding of cellular plasticity and stemness.

中文翻译：

---

肠肠内分泌谱系细胞具有稳态和损伤诱导的干细胞活性。

据报道，一些细胞群在稳态和损伤诱导的再生过程中具有肠干细胞（ISC）活性。在这里，我们通过比较 RNA 测序 (RNA-seq) 探索了假定的小鼠 ISC 群体之间的相互关系。多个循环 ISC 群体的转录组与 Lgr5 ⁺ ISC（定义最明确的 ISC 池）非常相似，但 Bmi1-GFP ⁺细胞截然不同，并且富含肠内分泌 (EE) 标记，包括 Prox1。Prox1-GFP ⁺细胞在体外表现出持续的克隆生长，Prox1 ⁺细胞的谱系追踪显示在体内稳态期间和辐射诱导损伤后具有长寿命的克隆。单细胞 mRNA-seq 显示 Prox1-GFP ⁺细胞的两个子集，其中一个类似于成熟的 EE 细胞，而另一个则显示低水平 EE 基因表达，但共表达簇细胞标记物 Lgr5 和 Ascl2，让人想起标记保留分泌祖细胞。我们的数据表明，EE 谱系，包括成熟的 EE 细胞，包含稳态和损伤诱导 ISC 的库，扩展了我们对细胞可塑性和干性的理解。