Journal
CELL STEM CELL
Volume 17, Issue 1, Pages 101-115Publisher
CELL PRESS
DOI: 10.1016/j.stem.2015.05.015
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Funding
- National Cancer Institute (NCI) [CA21765]
- NIH [EY014867, EY018599, CA168875]
- American Lebanese Syrian Associated Charities (ALSAC)
- Alex's Lemonade Stand Foundation for Childhood Cancer
- NCI [RO1CA20525, T32 CA009657]
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Cell-based therapies to treat retinal degeneration are now being tested in clinical trials. However, it is not known whether the source of stem cells is important for the production of differentiated cells suitable for transplantation. To test this, we generated induced pluripotent stem cells (iPSCs) from murine rod photoreceptors (r-iPSCs) and scored their ability to make retinae by using a standardized quantitative protocol called STEM-RET. We discovered that r-iPSCs more efficiently produced differentiated retinae than did embryonic stem cells (ESCs) or fibroblast-derived iPSCs (f-iPSCs). Retinae derived from f-iPSCs had fewer amacrine cells and other inner nuclear layer cells. Integrated epigenetic analysis showed that DNA methylation contributes to the defects in f-iPSC retinogenesis and that rod-specific CTCF insulator protein-binding sites may promote r-iPSC retinogenesis. Together, our data suggest that the source of stem cells is important for producing retinal neurons in three-dimensional (3D) organ cultures.
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