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Development. 2014 Sep;141(18):3472-82. doi: 10.1242/dev.109892. Epub 2014 Aug 19.

Exclusive multipotency and preferential asymmetric divisions in post-embryonic neural stem cells of the fish retina.

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Centre for Organismal Studies (COS) Heidelberg, Im Neuenheimer Feld 230, Heidelberg 69120, Germany
Centre for Organismal Studies (COS) Heidelberg, Im Neuenheimer Feld 230, Heidelberg 69120, Germany.
Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
Cavendish Laboratory, Department of Physics, JJ Thomson Avenue, University of Cambridge, Cambridge CB3 0HE, UK The Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.


The potency of post-embryonic stem cells can only be addressed in the living organism, by labeling single cells after embryonic development and following their descendants. Recently, transplantation experiments involving permanently labeled cells revealed multipotent neural stem cells (NSCs) of embryonic origin in the medaka retina. To analyze whether NSC potency is affected by developmental progression, as reported for the mammalian brain, we developed an inducible toolkit for clonal labeling and non-invasive fate tracking. We used this toolkit to address post-embryonic stem cells in different tissues and to functionally differentiate transient progenitor cells from permanent, bona fide stem cells in the retina. Using temporally controlled clonal induction, we showed that post-embryonic retinal NSCs are exclusively multipotent and give rise to the complete spectrum of cell types in the neural retina. Intriguingly, and in contrast to any other vertebrate stem cell system described so far, long-term analysis of clones indicates a preferential mode of asymmetric cell division. Moreover, following the behavior of clones before and after external stimuli, such as injuries, shows that NSCs in the retina maintained the preference for asymmetric cell division during regenerative responses. We present a comprehensive analysis of individual post-embryonic NSCs in their physiological environment and establish the teleost retina as an ideal model for studying adult stem cell biology at single cell resolution.


Asymmetric division; Medaka; Multipotency; Neural progenitor cells; Neural stem cells; Retina

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