Generation of Rx+/Pax6+ neural retinal precursors from embryonic stem cells

Hanako Ikeda, Fumitaka Osakada, Kiichi Watanabe, Kenji Mizuseki, Tomoko Haraguchi, Hiroyuki Miyoshi, Daisuke Kamiya, Yoshihito Honda, Noriaki Sasai, Nagahisa Yoshimura, Masayo Takahashi, Yoshiki Sasai

Research output: Contribution to journalArticlepeer-review

287 Citations (Scopus)

Abstract

We report directed differentiaion of retinal precursors in vitro from mouse ES cells. Six3+ rostral brain progenitors are generated by culturing ES cells under serum-free suspension conditions (SFEB culture) in the presence of Wnt and Nodal antagonists (Dkk1 and LeftyA), and subsequently steered to differentiate into Rx+ cells (16%) by treatment with activin and serum. Consistent with the characteristics of early neural retinal precursors, the induced Rx+ cells coexpress Pax6 and the mitotic marker Ki67, but not Nestin. The ES cell-derived precursors efficiently generate cells with the photoreceptor phenotype (rhodopsin+, recoverin+) when cocultured with embryonic retinal cells. Furthermore, organotypic culture studies demonstrate the selective integration and survival of ES cell-derived cells with the photoreceptor phenotype (marker expression and morphology) in the outer nuclear layer of the retina. Taken together, ES cells treated with SFEB/Dkk1/LeftyA/serum/activin generate neural retinal precursors, which have the competence of photoreceptor differentiation.

Original languageEnglish
Pages (from-to)11331-11336
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number32
DOIs
Publication statusPublished - 09-08-2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

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