In mice, intestinal tuft cells have been described as a long-lived, postmitotic cell type. Two distinct subsets have been identified: tuft-1 and tuft-2 (ref. ¹). By combining analysis of primary human intestinal resection material and intestinal organoids, we identify four distinct human tuft cell states, two of which overlap with their murine counterparts. We show that tuft cell development depends on the presence of Wnt ligands, and that tuft cell numbers rapidly increase on interleukin-4 (IL-4) and IL-13 exposure, as reported previously in mice^2,3,4. This occurs through proliferation of pre-existing tuft cells, rather than through increased de novo generation from stem cells. Indeed, proliferative tuft cells occur in vivo both in fetal and in adult human intestine. Single mature proliferating tuft cells can form organoids that contain all intestinal epithelial cell types. Unlike stem and progenitor cells, human tuft cells survive irradiation damage and retain the ability to generate all other epithelial cell types. Accordingly, organoids engineered to lack tuft cells fail to recover from radiation-induced damage. Thus, tuft cells represent a damage-induced reserve intestinal stem cell pool in humans.

在小鼠中，肠道簇状细胞被描述为一种长寿的有丝分裂后细胞类型。已经确定了两个不同的亚群：tuft-1 和 tuft-2（参考文献 ¹）。通过结合原代人类肠道切除材料和肠道类器官的分析，我们确定了四种不同的人类簇状细胞状态，其中两种与小鼠对应物重叠。我们表明，簇状细胞发育取决于 Wnt 配体的存在，并且簇状细胞数量在白细胞介素 4 （IL-4） 和 IL-13 暴露时迅速增加，如之前在小鼠中报道的那样^2,3,4。这是通过预先存在的簇状细胞增殖来实现的，而不是通过干细胞从头生成的增加来实现的。事实上，增殖性簇状细胞在体内存在于胎儿和成人肠道中。单个成熟的增殖簇状细胞可以形成包含所有肠上皮细胞类型的类器官。与干细胞和祖细胞不同，人类簇状细胞在受到辐射损伤后存活下来，并保留了产生所有其他上皮细胞类型的能力。因此，被改造为缺乏簇状细胞的类器官无法从辐射诱导的损伤中恢复。因此，簇状细胞代表了人类损伤诱导的储备肠道干细胞库。