Generation of a ciliary margin-like stem cell niche from self-organizing human retinal tissue
| Autor: | Atsushi Kuwahara, Yoshiki Sasai, Tokushige Nakano, Koichi Saito, Chikafumi Ozone, Mototsugu Eiraku |
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| Rok vydání: | 2014 |
| Předmět: |
Cellular differentiation
Cell Culture Techniques General Physics and Astronomy Bone Morphogenetic Protein 4 Retinal Pigment Epithelium Biology Fibroblast growth factor General Biochemistry Genetics and Molecular Biology Retina Glycogen Synthase Kinase 3 Mice medicine Animals Humans Cell Lineage Receptor Fibroblast Growth Factor Type 1 Progenitor cell Stem Cell Niche Embryonic Stem Cells Mice Inbred ICR Multidisciplinary Cilium Multipotent Stem Cells Cell Differentiation General Chemistry Flow Cytometry Embryonic stem cell Immunohistochemistry Cell biology medicine.anatomical_structure Cell culture Female Stem cell |
| Zdroj: | Nature communications. 6 |
| ISSN: | 2041-1723 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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