TY - JOUR
T1 - Toward the generation of rod and cone photoreceptors from mouse, monkey and human embryonic stem cells
AU - Osakada, Fumitaka
AU - Ikeda, Hanako
AU - Mandai, Michiko
AU - Wataya, Takafumi
AU - Watanabe, Kiichi
AU - Yoshimura, Nagahisa
AU - Akaike, Akiori
AU - Sasai, Yoshiki
AU - Takahashi, Masayo
N1 - Funding Information:
We thank J. Takahashi (Kyoto University, Kyoto, Japan) for providing the monkey ES cell line, H. Suemori and N. Nakatsuji (Kyoto University) for providing the human ES cell line, S. Nakagawa (RIKEN, Japan), T. Kume, H. Katsuki (Kyoto University), M. Haruta and M. Akimoto (Kyoto University Hospital) for valuable comments on this work, S. Nishikawa, M. Osawa and T. Era (RIKEN) for advice on FACS, K. Iseki and S. Yonemura (Riken) for the electron microscopic analysis, T. Yokota, A. Nomori, N. Ishibashi and A. Nishiyama for excellent technical assistance, and members of the Takahashi laboratory, the Sasai laboratory and the Akaike laboratory for discussions. This work was supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology, and the Leading Project (M.T. and Y.S.). This study was also supported by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science, and the Mochida Memorial Foundation for Medical and Pharmaceutical Research (F.O.).
PY - 2008/2
Y1 - 2008/2
N2 - We previously reported the differentiation of mouse embryonic stem (ES) cells into retinal progenitors. However, these progenitors rarely differentiate into photoreceptors unless they are cultured with embryonic retinal tissues. Here we show the in vitro generation of putative rod and cone photoreceptors from mouse, monkey and human ES cells by stepwise treatments under defined culture conditions, in the absence of retinal tissues. With mouse ES cells, Crx+ photoreceptor precursors were induced from Rx+ retinal progenitors by treatment with a Notch signal inhibitor. Further application of fibroblast growth factors, Shh, taurine and retinoic acid yielded a greater number of rhodopsin+ rod photoreceptors, in addition to default cone production. With monkey and human ES cells, feeder- and serum-free suspension culture combined with Wnt and Nodal inhibitors induced differentiation of Rx+ or Mitf+ retinal progenitors, which produced retinal pigment epithelial cells. Subsequent treatment with retinoic acid and taurine induced photoreceptor differentiation. These findings may facilitate the development of human ES cell-based transplantation therapies for retinal diseases.
AB - We previously reported the differentiation of mouse embryonic stem (ES) cells into retinal progenitors. However, these progenitors rarely differentiate into photoreceptors unless they are cultured with embryonic retinal tissues. Here we show the in vitro generation of putative rod and cone photoreceptors from mouse, monkey and human ES cells by stepwise treatments under defined culture conditions, in the absence of retinal tissues. With mouse ES cells, Crx+ photoreceptor precursors were induced from Rx+ retinal progenitors by treatment with a Notch signal inhibitor. Further application of fibroblast growth factors, Shh, taurine and retinoic acid yielded a greater number of rhodopsin+ rod photoreceptors, in addition to default cone production. With monkey and human ES cells, feeder- and serum-free suspension culture combined with Wnt and Nodal inhibitors induced differentiation of Rx+ or Mitf+ retinal progenitors, which produced retinal pigment epithelial cells. Subsequent treatment with retinoic acid and taurine induced photoreceptor differentiation. These findings may facilitate the development of human ES cell-based transplantation therapies for retinal diseases.
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U2 - 10.1038/nbt1384
DO - 10.1038/nbt1384
M3 - Article
C2 - 18246062
AN - SCOPUS:38949157774
SN - 1087-0156
VL - 26
SP - 215
EP - 224
JO - Nature Biotechnology
JF - Nature Biotechnology
IS - 2
ER -