title: Identification, visualization and clonal analysis of intestinal stem cells in fish.
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.
authors: Centre for Organismal Studies (COS), Heidelberg University, 69120 Heidelberg, Germany.
authors: Narges
authors: 0000-0002-9890-3229
authors: N
authors: Aghaallaei
authors: Centre for Organismal Studies (COS), Heidelberg University, 69120 Heidelberg, Germany.
authors: Franziska
authors: F
authors: Gruhl
authors: Centre for Organismal Studies (COS), Heidelberg University, 69120 Heidelberg, Germany.
authors: Colin Q
authors: CQ
authors: Schaefer
authors: Centre for Organismal Studies (COS), Heidelberg University, 69120 Heidelberg, Germany Laboratory for applications of synchrotron radiation, Karslruhe Institute for Technology (KIT), 76131 Karlsruhe, Germany.
authors: Tobias
authors: T
authors: Wernet
authors: Centre for Organismal Studies (COS), Heidelberg University, 69120 Heidelberg, Germany Laboratory for applications of synchrotron radiation, Karslruhe Institute for Technology (KIT), 76131 Karlsruhe, Germany.
authors: Venera
authors: V
authors: Weinhardt
authors: Centre for Organismal Studies (COS), Heidelberg University, 69120 Heidelberg, Germany.
authors: Lázaro
authors: L
authors: Centanin
authors: Laboratory for applications of synchrotron radiation, Karslruhe Institute for Technology (KIT), 76131 Karlsruhe, Germany.
authors: Felix
authors: F
authors: Loosli
authors: Laboratory for applications of synchrotron radiation, Karslruhe Institute for Technology (KIT), 76131 Karlsruhe, Germany.
authors: Tilo
authors: T
authors: Baumbach
authors: Centre for Organismal Studies (COS), Heidelberg University, 69120 Heidelberg, Germany jochen.wittbrodt@cos.uni-heidelberg.de narges.aghaallaei@cos.uni-heidelberg.de.
authors: Joachim
authors: 0000-0001-8550-7377
authors: J
authors: Wittbrodt
mesh_terms: D000818:Animals; D005399:Fishes; D041981:Gastrointestinal Tract / Q000166:cytology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D007422:Intestines / Q000166:cytology*; D009990:Oryzias / Q000378:metabolism; D010802:Phylogeny; D055153:Stem Cell Niche / Q000502:physiology; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D055114:X-Ray Microtomography
keywords: Cell division mode; Digestive tract; Intestinal stem cells; Medaka