Generation of Rx+/Pax6+
neural retinal precursors from embryonic stem cells
Ikeda H, Osakada F, Watanabe K, Mizuseki K, Haraguchi T, Miyoshi H, Kamiya
D, Honda Y, Sasai N, Yoshimura N, Takahashi M and Sasai Y
Proc Natl Acad Sci U S A 102(32):11331-6 (2005)
SUMMARY
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.
LINK
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16076961