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Human iPS cells engender corneal epithelial stem cells with holoclone-forming capabilities.

iScience (2021-07-02)
Shinya Watanabe, Ryuhei Hayashi, Yuzuru Sasamoto, Motokazu Tsujikawa, Bruce R Ksander, Markus H Frank, Andrew J Quantock, Natasha Y Frank, Kohji Nishida
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.

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Sigma-Aldrich
3,3′,5-Triiodo-L-thyronine sodium salt, γ-irradiated, powder, suitable for, suitable for cell culture