Generation of functional eyes from pluripotent cells

PLoS Biol. 2009 Aug;7(8):e1000174. doi: 10.1371/journal.pbio.1000174. Epub 2009 Aug 18.

Abstract

Pluripotent cells such as embryonic stem (ES) and induced pluripotent stem (iPS) cells are the starting point from which to generate organ specific cell types. For example, converting pluripotent cells to retinal cells could provide an opportunity to treat retinal injuries and degenerations. In this study, we used an in vivo strategy to determine if functional retinas could be generated from a defined population of pluripotent Xenopus laevis cells. Animal pole cells isolated from blastula stage embryos are pluripotent. Untreated, these cells formed only epidermis, when transplanted to either the flank or eye field. In contrast, misexpression of seven transcription factors induced the formation of retinal cell types. Induced retinal cells were committed to a retinal lineage as they formed eyes when transplanted to the flanks of developing embryos. When the endogenous eye field was replaced with induced retinal cells, they formed eyes that were molecularly, anatomically, and electrophysiologically similar to normal eyes. Importantly, induced eyes could guide a vision-based behavior. These results suggest the fate of pluripotent cells may be purposely altered to generate multipotent retinal progenitor cells, which differentiate into functional retinal cell classes and form a neural circuitry sufficient for vision.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Culture Techniques
  • Cell Differentiation*
  • Eye / anatomy & histology
  • Eye / cytology
  • Eye / growth & development
  • Gene Expression Regulation*
  • Humans
  • Neurons / cytology
  • Pluripotent Stem Cells / cytology*
  • Pluripotent Stem Cells / metabolism
  • Pluripotent Stem Cells / transplantation
  • Regenerative Medicine
  • Retina / cytology*
  • Retina / growth & development
  • Stem Cell Transplantation
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Xenopus laevis / embryology

Substances

  • Transcription Factors