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

Watanabe, Shinya, Hayashi, Ryuhei, Sasamoto, Yuzuru, Tsujikawa, Motokazu, Ksander, Bruce R., Frank, Markus H., Quantock, Andrew J. ORCID: https://orcid.org/0000-0002-2484-3120, Frank, Natasha Y. and Nishida, Kohji 2021. Human iPS cells engender corneal epithelial stem cells with holoclone-forming capabilities. iScience 24 (6) , 102688. 10.1016/j.isci.2021.102688

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Optometry and Vision Sciences
Publisher:	Cell Press
ISSN:	2589-0042
Date of First Compliant Deposit:	21 February 2023
Date of Acceptance:	2 June 2021
Last Modified:	03 May 2023 08:22
URI:	https://orca.cardiff.ac.uk/id/eprint/157170

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