Abstract
Recently, a stochastic model of symmetrical stem cell division followed by neutral drift has been proposed for intestinal stem cells (ISCs), which 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 an asymmetric division mode. To address whether the mode of stem cell division follows phylogenetic or ontogenetic routes, we analysed the entire gastrointestinal tract of the teleost medaka (Oryzias latipes). X-ray microcomputed tomography shows a correlation of 3D topography with the functional domains. 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 that is functionally equivalent to mammalian intestinal crypts. Stem cells in this compartment are characterized by the expression of homologs of mammalian ISC markers – sox9, axin2 and lgr5 – emphasizing the evolutionary conservation of the Wnt pathway components in the stem cell niche of the intestine. 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.
Highlights
Recent key findings have stimulated the debate about the division mode of adult stem cells in mammals in particular and vertebrates in general
The entire intestine is in continuous growth and homeostasis and all differentiated cell types originating from intestinal stem cells (ISCs) are shed into the intestinal lumen (Fig. 7)
ISCs reside in the furrows at the base of intestinal folds and express typical stem cell markers including lgr5 (Leushacke et al, 2013; Lim et al, 2013) that we discovered in the medaka gut
Summary
Recent key findings have stimulated the debate about the division mode of adult stem cells (symmetric vs. asymmetric) in mammals in particular and vertebrates in general. While on the one hand prominent symmetric cell divisions followed by neutral drift are best explaining the division of multi--‐ potent ISCs in mouse (Snippert et al, 2010), the preferential asymmetric division mode of multi--‐ potent stem cells is driving functional homeostasis during retinal growth in the teleost retina (Centanin et al, 2014). This poses the question whether there is an ancestral (asymmetric) and derived (symmetric) mode of stem cell progression. Similar to the mammalian intestine, the inner layer of the intestine is folded in many fish species, intestinal folds are often less distinct, while villi and crypts as in mammals are not described for medaka or zebrafish
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