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Generation of a ciliary margin-like stem cell niche from self-organizing human retinal tissue

Author

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  • Atsushi Kuwahara

    (Neurogenesis and Organogenesis Group, RIKEN Center for Developmental Biology, 2-2-3 Manatojima-Minamimachi, Chuo, Kobe 650-0047, Japan
    Human Stem Cell Technology Unit, RIKEN Center for Developmental Biology
    Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd.
    Present address: Regenerative & Cellular Medicine Office, Sumitomo Dainippon Pharma Co., Ltd., 2-2-2, Minatojima-minamimachi, Chuo, Kobe 650-0047, Japan)

  • Chikafumi Ozone

    (Neurogenesis and Organogenesis Group, RIKEN Center for Developmental Biology, 2-2-3 Manatojima-Minamimachi, Chuo, Kobe 650-0047, Japan
    Graduate School of Medicine, Nagoya University)

  • Tokushige Nakano

    (Neurogenesis and Organogenesis Group, RIKEN Center for Developmental Biology, 2-2-3 Manatojima-Minamimachi, Chuo, Kobe 650-0047, Japan
    Human Stem Cell Technology Unit, RIKEN Center for Developmental Biology
    Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd.)

  • Koichi Saito

    (Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd.)

  • Mototsugu Eiraku

    (Four-Dimensional Tissue Analysis Unit, RIKEN Center for Developmental Biology)

  • Yoshiki Sasai

    (Neurogenesis and Organogenesis Group, RIKEN Center for Developmental Biology, 2-2-3 Manatojima-Minamimachi, Chuo, Kobe 650-0047, Japan
    Human Stem Cell Technology Unit, RIKEN Center for Developmental Biology)

Abstract

In the developing neural retina (NR), multipotent stem cells within the ciliary margin (CM) contribute to de novo retinal tissue growth. We recently reported the ability of human embryonic stem cells (hESCs) to self-organize stratified NR using a three-dimensional culture technique. Here we report the emergence of CM-like stem cell niches within human retinal tissue. First, we developed a culture method for selective NR differentiation by timed BMP4 treatment. We then found that inhibiting GSK3 and FGFR induced the transition from NR tissue to retinal pigment epithelium (RPE), and that removing this inhibition facilitated the reversion of this RPE-like tissue back to the NR fate. This step-wise induction-reversal method generated tissue aggregates with RPE at the margin of central-peripherally polarized NR. We demonstrate that the NR–RPE boundary tissue further self-organizes a niche for CM stem cells that functions to expand the NR peripherally by de novo progenitor generation.

Suggested Citation

  • Atsushi Kuwahara & Chikafumi Ozone & Tokushige Nakano & Koichi Saito & Mototsugu Eiraku & Yoshiki Sasai, 2015. "Generation of a ciliary margin-like stem cell niche from self-organizing human retinal tissue," Nature Communications, Nature, vol. 6(1), pages 1-15, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7286
    DOI: 10.1038/ncomms7286
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    Cited by:

    1. Birthe Dorgau & Joseph Collin & Agata Rozanska & Darin Zerti & Adrienne Unsworth & Moira Crosier & Rafiqul Hussain & Jonathan Coxhead & Tamil Dhanaseelan & Aara Patel & Jane C. Sowden & David R. FitzP, 2024. "Single-cell analyses reveal transient retinal progenitor cells in the ciliary margin of developing human retina," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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