Department of Orofacial Sciences and Program in Craniofacial Biology, University of California, San Francisco, San Francisco, CA, USA.
Department of Medicine, University of Western Ontario, London, ON, Canada.
EMBO J. 2019 Feb 15;38(4). doi: 10.15252/embj.201899984. Epub 2019 Jan 11.
During homeostasis, the colonic epithelium is replenished every 3-5 days by rapidly cycling stem cells. However, various insults can lead to depletion of stem cells, and colonic epithelium can be regenerated from negative cells. While studies in the small intestine have addressed the lineage identity of the negative regenerative cell population, in the colon this question has remained unanswered. Here, we set out to identify which cell(s) contribute to colonic regeneration by performing genetic fate-mapping studies of progenitor populations in mice. First, using -19 () to mark a heterogeneous population of cells, we found that negative cells can regenerate colonic crypts and give rise to stem cells. absorptive progenitor cells did not contribute to epithelial repair after injury, whereas secretory progenitors did contribute to this process. Additionally, while colonic cells contributed minimally to other lineages during homeostasis, they displayed plasticity and contributed to epithelial repair during injury, independent of cells. Our findings suggest that promotion of secretory progenitor plasticity could enable gut healing in colitis.
在体内平衡期间，结肠上皮细胞通过快速循环的干细胞每 3-5 天更新一次。然而，各种损伤会导致干细胞耗竭，而结肠上皮可以由阴性细胞再生。虽然小肠的研究已经解决了阴性再生细胞群的谱系身份问题，但在结肠中，这个问题仍未得到解答。在这里，我们通过对小鼠中祖细胞群体进行遗传谱系追踪研究，着手确定哪些细胞有助于结肠再生。首先，我们使用 -19 () 标记异质性细胞群体，发现阴性细胞可以再生结肠隐窝并产生干细胞。吸收祖细胞在损伤后不会促进上皮修复，而分泌祖细胞则会促进这一过程。此外，虽然结肠 细胞在体内平衡期间对其他谱系的贡献很小，但它们在损伤期间表现出可塑性，并独立于 细胞促进上皮修复。我们的发现表明，促进分泌祖细胞的可塑性可能使结肠炎中的肠道愈合成为可能。
