Human iPS cells engender corneal epithelial stem cells with holoclone-forming capabilities
Authors
Shinya Watanabe, Ryuhei Hayashi, Yuzuru Sasamoto, Motokazu Tsujikawa, Bruce R. Ksander, Markus H. Frank, Andrew J. Quantock, Natasha Y. Frank, Kohji Nishida
Institution
Osaka University
Country
Japan
Year
2021
Journal
iScience
Abstract
Human induced pluripotent stem cells (hiPSCs) can generate a multiplicity of organoids, yet no compelling evidence currently exists as to whether or not these contain tissue-specific, holoclone-forming stem cells. Here, we show that a subpopulation of cells in a hiPSC-derived corneal epithelial cell sheet is positive for ABCB5 (ATP-binding cassette, sub-family B, member 5), a functional marker of adult corneal epithelial stem cells. These cells possess remarkable holoclone-forming capabilities, which can be suppressed by an antibody-mediated ABCB5 blockade. The cell sheets are generated from ABCB5+ hiPSCs that first emerge in 2D eye-like organoids around six weeks of differentiation and display corneal epithelial immunostaining characteristics and gene expression patterns, including sustained expression of ABCB5. The findings highlight the translational potential of ABCB5-enriched, hiPSC-derived corneal epithelial cell sheets to recover vision in stem cell-deficient human eyes and represent the first report of holoclone-forming stem cells being directly identified in an hiPSC-derived organoid.