Bone morphogenetic proteins and secreted frizzled related protein 2 maintain the quiescence of adult mammalian retinal stem cells

Authors

  • Laurent Balenci,

    Corresponding author
    1. Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research University of Toronto, Toronto, Ontario, Canada
    • Correspondence: Laurent Balenci, Ph.D., Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 3E1, Canada. Telephone: +1-416-978-4539; Fax: +1-416-978-2666; e-mail: laurent.balenci@utoronto.ca

    Search for more papers by this author
  • Carl Wonders,

    1. Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research University of Toronto, Toronto, Ontario, Canada
    Search for more papers by this author
  • Brenda L.K. Coles,

    1. Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research University of Toronto, Toronto, Ontario, Canada
    Search for more papers by this author
  • Laura Clarke,

    1. Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research University of Toronto, Toronto, Ontario, Canada
    Search for more papers by this author
  • Derek van der Kooy


  • Author contributions: L.B.: conception and design, collection and assembly of data, data analysis and interpretation, and manuscript writing; C.W.: collection and assembly of data, data analysis and interpretation, and manuscript writing; B.C. and L.C.: collection and assembly of data; D.V.D.K.: financial support, data analysis and interpretation, manuscript writing, and final approval of manuscript.

Abstract

Rare retinal stem cells (RSCs) within the ciliary epithelium at the retinal margin of the adult mouse and human eyes can divide in vitro in the absence of growth factors to generate clonal, self-renewing spheres which can generate all the retinal cell types. Since no regenerative properties are seen in situ in the adult mammalian eye, we sought to determine the factors that are involved in the repression of endogenous RSCs. We discovered that factors secreted by the adult lens and cornea block the proliferation of adult RSCs in vitro. Bone morphogenetic protein (BMP)2, BMP4, and secreted frizzled related protein 2 were identified as principal effectors of the anti-proliferative effects on RSCs. As a similar induced quiescence was observed in vitro on both mouse and human RSCs, targeting these molecules in vivo may reactivate RSCs directly in situ in the eyes of the blind. Stem Cells 2013;31:2218–2230

Ancillary