A Comparative Transcriptomic Analysis Reveals Conserved Features of Stem Cell Pluripotency in Planarians and Mammals§

Authors

  • Roselyne M. Labbé,

    1. The Hospital for Sick Children, Program in Developmental and Stem Cell Biology, University of Toronto, Toronto, Ontario, Canada
    2. Ontario Institute for Cancer Research, Toronto, Ontario, Canada
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  • Manuel Irimia,

    1. The Donnelly Centre, University of Toronto, Toronto, Ontario, Canada
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  • Ko W. Currie,

    1. The Hospital for Sick Children, Program in Developmental and Stem Cell Biology, University of Toronto, Toronto, Ontario, Canada
    2. Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada
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  • Alexander Lin,

    1. The Hospital for Sick Children, Program in Developmental and Stem Cell Biology, University of Toronto, Toronto, Ontario, Canada
    2. Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada
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  • Shu Jun Zhu,

    1. The Hospital for Sick Children, Program in Developmental and Stem Cell Biology, University of Toronto, Toronto, Ontario, Canada
    2. Ontario Institute for Cancer Research, Toronto, Ontario, Canada
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  • David D.R. Brown,

    1. The Hospital for Sick Children, Program in Developmental and Stem Cell Biology, University of Toronto, Toronto, Ontario, Canada
    2. Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada
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  • Eric J. Ross,

    1. Stowers Institute for Medical Research, Kansas City, Missouri, USA
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  • Veronique Voisin,

    1. The Donnelly Centre, University of Toronto, Toronto, Ontario, Canada
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  • Gary D. Bader,

    1. Ontario Institute for Cancer Research, Toronto, Ontario, Canada
    2. The Donnelly Centre, University of Toronto, Toronto, Ontario, Canada
    3. Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada
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  • Benjamin J. Blencowe,

    1. The Donnelly Centre, University of Toronto, Toronto, Ontario, Canada
    2. Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada
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  • Bret J. Pearson

    Corresponding author
    1. The Hospital for Sick Children, Program in Developmental and Stem Cell Biology, University of Toronto, Toronto, Ontario, Canada
    2. Ontario Institute for Cancer Research, Toronto, Ontario, Canada
    3. Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada
    • The Hospital for Sick Children, Program in Developmental and Stem Cell Biology, University of Toronto, Toronto, Ontario, Canada

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    • Telephone: 416-813-7654, ext. 28370; Fax: 416-813-8456


  • Author contributions: V.V. and G.D.B.: performed the GSEA; M.I.: performed all RNA-Seq-based comparisons with planarian and mammalian transcriptomes as well as the transcription factor analysis; E.J.R.: performed the transcriptome assembly; R.M.L.: performed all planarian gene cloning and most planarian experiments; B.J.P., A.L., S.J.Z., and K.W.C.: performed several individual RNAi experiments; D.D.R.B.: performed wild-type ISHs; B.J.P.: collected and purified all RNA from planarian tissue samples and wrote the manuscript; B.J.B.: edited the manuscript.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLSEXPRESS June 13, 2012.

Abstract

Many long-lived species of animals require the function of adult stem cells throughout their lives. However, the transcriptomes of stem cells in invertebrates and vertebrates have not been compared, and consequently, ancestral regulatory circuits that control stem cell populations remain poorly defined. In this study, we have used data from high-throughput RNA sequencing to compare the transcriptomes of pluripotent adult stem cells from planarians with the transcriptomes of human and mouse pluripotent embryonic stem cells. From a stringently defined set of 4,432 orthologs shared between planarians, mice and humans, we identified 123 conserved genes that are ≥5-fold differentially expressed in stem cells from all three species. Guided by this gene set, we used RNAi screening in adult planarians to discover novel stem cell regulators, which we found to affect the stem cell-associated functions of tissue homeostasis, regeneration, and stem cell maintenance. Examples of genes that disrupted these processes included the orthologs of TBL3, PSD12, TTC27, and RACK1. From these analyses, we concluded that by comparing stem cell transcriptomes from diverse species, it is possible to uncover conserved factors that function in stem cell biology. These results provide insights into which genes comprised the ancestral circuitry underlying the control of stem cell self-renewal and pluripotency. STEM Cells2012;30:1734–1745

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