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

Aghaallaei, Narges; Gruhl, Franziska; Schaefer, Colin Q.; Wernet, Tobias; Weinhardt, Venera; Centanin, Lázaro; Loosli, Felix; Baumbach, Tilo; Wittbrodt, Joachim

doi:10.1242/dev.134098

Cited by 51 publications

(53 citation statements)

References 69 publications

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“…Experimentally, clones were generated using the Gaudí toolkit, which consists of transgenic lines bearing floxed fluorescent reporter cassettes (Gaudí RSG or Gaudí BBW2.1 ) and allows inducing either the expression or the activity of the Cre recombinase (Gaudí Hsp70A.CRE or Gaudí Ubiq.iCRE , respectively). The Gaudí toolkit has already been extensively used for lineage analyses in medaka (Centanin et al , 2014; Reinhardt et al , 2015; Lust et al , 2016; Aghaallaei et al , 2016; Seleit et al , 2017). Clones are generated by applying subtle heat-shock treatments (when Gaudí Hsp70A.CRE is used) or low doses of tamoxifen (when Gaudí Ubiq.iCRE is used) to double transgenic animals, which results in a sparse labelling of different cells along the fish body, transmitting the label to their offspring.…”

Section: Resultsmentioning

confidence: 99%

“…Since stem cells in fish maintain homeostasis and drive post-embryonic growth in a highly controlled manner, the system permits identifying similarities and differences in case both functions are performed by dedicated populations, or identifying conditions for homeostatic and growth outputs in case of a common stem cell. There are several genetic tools and techniques to explore aSCs in fish, and an abundant literature covering different aspects of their biology in various organs and also during regeneration paradigms (Gupta & Poss, 2012; Knopf et al , 2011; Tu & Johnson, 2011; Kizil et al , 2012; Kyritsis et al , 2012; Pan et al , 2013; Centanin et al , 2014; Jungke et al , 2015; Henninger et al , 2017; Singh et al , 2017; McKenna et al , 2016; Aghaallaei et al , 2016). Despite all these major advances, we still do not understand whether the same pool of stem cells is responsible for driving both growth and homeostatic replacement, or if alternatively, each task is performed by dedicated aSCs.…”

Section: Introductionmentioning

confidence: 99%

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Hierarchical Stem Cell Topography Splits Growth and Homeostatic Functions in the Fish Gill

Stolper¹,

Ambrosio²,

Danciu³

et al. 2018

Preprint

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1While lower vertebrates contain adult stem cells (aSCs) that maintain homeostasis and drive un-2 exhaustive organismal growth, mammalian aSCs display mainly the homeostatic function. 3Understanding aSC-driven growth is of paramount importance to promote organ regeneration and 4 prevent tumor formation in mammals. Here we present a clonal approach to address common or 5 dedicated populations of aSCs for homeostasis and growth. Our functional assays on medaka gills 6 demonstrate the existence of separate homeostatic and growth aSCs, which are clonal but differ in 7 their topology. While homeostatic aSCs are fixed, embedded in the tissue, growth aSCs locate at the 8 expanding peripheral zone. Modifications in tissue architecture can convert the homeostatic zone 9 into a growth zone, indicating a leading role for the physical niche defining stem cell output. We 10 hypothesize that physical niches are main players to restrict aSCs to a homeostatic function in 11 animals with a fixed adult size.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hierarchical Stem Cell Topography Splits Growth and Homeostatic Functions in the Fish Gill

Stolper¹,

Ambrosio²,

Danciu³

et al. 2018

Preprint

View full text Add to dashboard Cite

show abstract

“…High-resolution, and detailed scans of zebrafish and medaka have been accomplished through use of synchrotron radiation micro-computed tomography (SR microCT 30,31 , http://zfatlas.psu.edu/). However, limited access and cost for such beam sources makes this method impractical, especially when considering the large number of samples needed for phenotypic analysis and analysis of variation.…”

Section: Discussionmentioning

confidence: 99%

Utility of quantitative micro-computed tomographic analysis in zebrafish to define gene function during skeletogenesis

Charles

Sury

Tsang

et al. 2017

Bone

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The zebrafish is a powerful experimental model to investigate the genetic and morphologic basis of vertebrate development. Analysis of skeletogenesis in this fish is challenging as a result of the small size of the developing and adult zebrafish. Many of the bones of small fishes such as the zerbafish and medaka are quite thin, precluding many standard assays of bone quality and morphometrics commonly used on bones of larger animals. Microcomputed tomography (microCT) is a common imaging technique used for detailed analysis of the skeleton of the zebrafish and determination of mutant phenotypes. However, the utility of this modality for analysis of the zebrafish skeleton, and the effect of inherent variation among individual zebrafish, including variables such as sex, age and strain, is not well understood. Given the increased use and accessibility of microCT, we set out to define the sensitivity of microCT methods in developing and adult zebrafish. We assessed skeletal shape and density measures in the developing vertebrae and parasphenoid of the skull base. We found most skeletal variables are tightly correlated to standard length, but that at later growth stages (>3 months) there are age dependent effects on some skeletal measures. Further we find modest strain but not sex differences in skeletal measures. These data suggest that the appropriate control for assessing mutant phenotypes should be age and strain matched, ideally a wild-type sibling. By analyzing two mutants exhibiting skeletal dysplasia, we show that microCT imaging can be a sensitive method to quantify distinct skeletal parameters of adults. Finally, as developing zebrafish skeletons remain difficult to resolve by radiographic means, we define a contrast agent specific for bone that enhances resolution at early stages, permitting detailed morphometric analysis of the forming skeleton. This increased capability for detection extends the use of this imaging modality to leverage the zebrafish model to understand the development causes of skeletal dysplasias.

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“…The intestinal 12 epithelium has served as a fundamental model of how stem cells within a tissue are specified and 13 maintained. However, only few papers have detailed differentiation and stem cell biology and 14 differentiation in the intestine in fishes (Aghaallaei et al, 2016;Lickwar et al, 2017;Wallace et al, 15 2005;Zhao and Pack, 2017). To investigate the role of celsr1a in maintaining tissue homeostasis and 16 progenitor populations in adult tissues, we analyzed changes in the intestinal epithelium in the frnt 17 mutant.…”

Section: Identification Of the Genetic Cause Of Frnt Aging Phenotypes 19mentioning

confidence: 99%

Celsr1a is essential for tissue homeostasis and onset of aging phenotypes in the zebrafish

Barton

Henke

et al. 2019

Preprint

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The use of experimental genetics has been invaluable in defining the complex mechanisms by which aging and longevity are regulated. Zebrafish, while a prominent model for understanding the genetic basis of vertebrate development, have not been used systematically to address questions of how and why we age. In a mutagenesis screen focusing on late developmental phenotypes, we identified a new mutant, fruehrentner, that displays typical signs of aging already at young adult stages. We find that the phenotype is due to loss-of-function in the non-classical cadherin EGF LAG seven-pass G-type receptor 1a (celsr1a). The premature aging phenotype is not associated with increased cellular senescence or decreased telomere length but is a result of a broad failure to maintain progenitor cell populations in tissues. Through the analysis of a knockin reporter line, we find that celsr1a GFP is expressed broadly in early development but becomes restricted during maturation. We show that celsr1a is essential for maintenance of stem cell progenitors and leads to shifts in cell fate determination. Although celsr1a has many signaling functions including establishment of polarity within tissues, we show that caloric restriction can ameliorate the effect of celsr1a on lifespan in part through compensatory upregulation of celsr1 paralogues. These data suggest that celsr1a function helps to mediate stem cell maintenance during maturation and homeostasis of tissues and thus regulates the onset or expressivity of aging phenotypes.

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

Cited by 51 publications

References 69 publications

Hierarchical Stem Cell Topography Splits Growth and Homeostatic Functions in the Fish Gill

Hierarchical Stem Cell Topography Splits Growth and Homeostatic Functions in the Fish Gill

Utility of quantitative micro-computed tomographic analysis in zebrafish to define gene function during skeletogenesis

Celsr1a is essential for tissue homeostasis and onset of aging phenotypes in the zebrafish

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