Data from: Identification, visualization and clonal analysis of intestinal stem cells in fish

Recently, a stochastic model of symmetrical stem cell division followed by neutral drift has been proposed for intestinal stem cells (ISCs). This division mode has been suggested to represent the predominant mode of stem cell progression in mammals. In contrast, stem cells in the retina of teleost fish show a preferential asymmetric division mode. To address whether the mode of stem cell division is following phylogenetic or ontogenetic routes we characterized and analysed the entire gastrointestinal system with a particular focus on ISCs in the teleost medaka (Oryzias latipes). We analysed the entire intestine in adult medaka by X-ray micro-computed tomography within the intact body and combined that analysis with the cellular and molecular composition of the intestinal system. This allowed correlating the 3D topography with functional domains of the intestinal system. Morphology and gene expression data consistently argue for a subdivision of the medaka intestine into a small and large intestine. Analysis of ISCs in proliferation assays and via genetically encoded lineage-tracing highlights a stem cell niche in the furrow between the long intestinal folds. This niche is functionally equivalent to the mammalian intestinal crypts and stem cells in this compartment are characterized by the expression of sox9, axin2 as well as lgr5, homologs of mammalian ISC markers, emphasizing the evolutionary conservation of the Wnt-pathway components in the stem cell niche of the intestine. Consistent with a preferential symmetric division mode of medaka ISCs, the stochastic, sparse initial labelling of ISCs ultimately resulted in extended labelled or unlabelled domains originating from single stem cells in the furrow niche contributing to both, homeostasis and growth. Thus different modes of stem cell division co-evolved within one organism, and in the absence of physical isolation in crypts, ISCs contribute to homeostatic growth.近年来，有研究针对肠干细胞（intestinal stem cells，ISCs）提出了一种先经对称干细胞分裂、后伴随中性漂移的随机模型。该分裂模式被认为是哺乳动物干细胞增殖的主要方式。与之相反，硬骨鱼视网膜中的干细胞则表现出偏好性不对称分裂模式。为探究干细胞分裂模式是遵循系统发育还是个体发育路径，本研究对硬骨鱼青鳉（Oryzias latipes）的整个胃肠道系统进行了表征与分析，重点关注其中的肠干细胞。本研究通过X射线显微计算机断层扫描（X-ray micro-computed tomography）对完整活体中的成年青鳉全肠进行成像，并将该成像结果与肠道系统的细胞及分子组成分析相结合，由此可将三维形貌与肠道系统的功能区域进行关联分析。形态学与基因表达数据均支持将青鳉肠道划分为小肠与大肠的分类方式。通过增殖实验与遗传编码谱系示踪技术对肠干细胞进行分析，结果显示长肠道褶皱间的沟槽处存在干细胞微环境（stem cell niche）。该微环境在功能上与哺乳动物肠道隐窝相当，此区域内的干细胞以表达sox9、axin2及lgr5为特征，这些基因均为哺乳动物肠干细胞标记物的同源基因，这凸显了肠道干细胞微环境中Wnt通路（Wnt-pathway）组分的进化保守性。与青鳉肠干细胞偏好对称分裂模式的结论一致，对肠干细胞进行随机、稀疏的初始标记后，最终会形成由沟槽微环境中单个干细胞增殖而来的大面积标记或未标记区域，这些区域同时参与稳态维持与机体生长。由此可见，不同的干细胞分裂模式在同一生物体内协同进化；在缺乏隐窝式物理隔离的情况下，肠干细胞可参与稳态性生长过程。