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The abrogation of condensin function provides independent evidence for defining the self-renewing population of pluripotent stem cells

View ORCID ProfileAlvina G. Lai, Nobuyoshi Kosaka, Prasad Abnave, Sounak Sahu, View ORCID ProfileA. Aziz Aboobaker
doi: https://doi.org/10.1101/143339
Alvina G. Lai
Department of Zoology, Tinbergen Building, South Parks Road, University of Oxford, Oxford OX1 3PS, United Kingdom
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Nobuyoshi Kosaka
Department of Zoology, Tinbergen Building, South Parks Road, University of Oxford, Oxford OX1 3PS, United Kingdom
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Prasad Abnave
Department of Zoology, Tinbergen Building, South Parks Road, University of Oxford, Oxford OX1 3PS, United Kingdom
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Sounak Sahu
Department of Zoology, Tinbergen Building, South Parks Road, University of Oxford, Oxford OX1 3PS, United Kingdom
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A. Aziz Aboobaker
Department of Zoology, Tinbergen Building, South Parks Road, University of Oxford, Oxford OX1 3PS, United Kingdom
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Abstract

Heterogeneity of planarian neoblast stem cells has been categorised on the basis of single cell expression analyses and subsequent experiments to demonstrate lineage relationships. Some data suggest that despite gene expression heterogeneity amongst cells in the cell cycle, in fact only one sub-population, known as sigma neoblasts, can self-renew. Without the tools to perform live in vivo lineage analysis, we instead took an alternative approach to provide independent evidence for defining the self-renewing stem cell population. We exploited the role of highly conserved condensin proteins to functionally assay neoblast self-renewal properties. Condensins are involved in forming properly condensed chromosomes to allow cell division to proceed during mitosis, and their abrogation inhibits mitosis and can lead to repeated endoreplication of the genome in cells that make repeated attempts to divide. We find that planarians possess only the condensin I complex, and that this is required for normal stem cell function. Abrogation of condensin function led to rapid stem cell depletion accompanied by the appearance of giant cells with increased DNA content. Using previously discovered markers of heterogeneity we show that enlarged cells are always from the sigma-class of the neoblast population and we never observe evidence for endoreplication for the other neoblast subclasses. Overall, our data establish that condensins are essential for stem cell maintenance and provide independent evidence that only sigma-neoblasts are capable of multiple rounds of cell division and hence self-renewal.

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Posted May 29, 2017.
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The abrogation of condensin function provides independent evidence for defining the self-renewing population of pluripotent stem cells
Alvina G. Lai, Nobuyoshi Kosaka, Prasad Abnave, Sounak Sahu, A. Aziz Aboobaker
bioRxiv 143339; doi: https://doi.org/10.1101/143339
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The abrogation of condensin function provides independent evidence for defining the self-renewing population of pluripotent stem cells
Alvina G. Lai, Nobuyoshi Kosaka, Prasad Abnave, Sounak Sahu, A. Aziz Aboobaker
bioRxiv 143339; doi: https://doi.org/10.1101/143339

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