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标题：Human iPS cells engender corneal epithelial stem cells with holoclone-forming capabilities
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作者：Shinya Watanabe ; Ryuhei Hayashi ; Yuzuru Sasamoto 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：6
页码：1-14
DOI：10.1016/j.isci.2021.102688
语种：English
出版社：Elsevier
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;