摘要：SummaryHuman 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.Graphical abstractDisplay OmittedHighlights•Human iPS cell-derived corneal epithelia contain ABCB5-positive stem cells•The ABCB5-positive cells possess holoclone-forming capabilities•An antibody-mediated ABCB5 blockade suppresses holoclone formation•Holoclone-forming stem cells are present in a human iPS cell-derived tissue constructBioengineering; Cell biology; Stem cells research; Tissue engineering;
