Document Type
Journal Article
Publication Title
iScience
Volume
24
Issue
6
Publisher
Elsevier
School
School of Medical and Health Sciences
RAS ID
38932
Funders
Japan Agency for Medical Research and Development Ministry of Education, Culture, Sports, Science and Technology of Japan Osaka Eye Bank Research Grant International Joint Research Promotion Program of Osaka University
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.
DOI
10.1016/j.isci.2021.102688
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Comments
Watanabe, S., Hayashi, R., Sasamoto, Y., Tsujikawa, M., Ksander, B. R., Frank, M. H., ... Nishida, K. (2021). Human iPS cells engender corneal epithelial stem cells with holoclone-forming capabilities. iScience, 24(6), article 102688. https://doi.org/10.1016/j.isci.2021.102688