Limbal BCAM expression identifies a proliferative progenitor population capable of holoclone formation and corneal differentiation

Authors

Yuzuru Sasamoto
Catherine A. A. Lee
Brian J. Wilson
Florian Buerger
Gabrielle Martin
Ananda Mishra
Shoko Kiritoshi
Johnathan Tran
Gabriel Gonzalez
Friedhelm Hildebrandt
Vickie Y. Jo
Christine G. Lian
George F. Murphy
Bruce R. Ksander
Markus H. Frank, Edith Cowan UniversityFollow
Natasha Y. Frank

Document Type

Journal Article

Publication Title

Cell Reports

Volume

40

Issue

6

PubMed ID

35947947

Publisher

Elsevier

School

School of Medical and Health Sciences

RAS ID

52089

Funders

NIH/NEI grants 1K99EY031741 to Y.S. and 1R01EY025794 and R24EY028767 to N.Y.F., B.R.K., and M.H.F. / NIH/NEI Schepens Core grant P30EY003790 to B.R.K. / NIH/NHLBI grant 1R01HL161087 to G.F.M., M.H.F., and N.Y.F. / NIH/NIBIB grant 2T32EB016652-06 to C.A.A.L. / NIH/NIDDK R01-DK076683 to F.H. / Alcon Young Investigator Grant and Japan Eye Bank Association Overseas Award to Y.S. / VA R&D Merit Review Award 1I01RX000989 and a Harvard Stem Cell Institute seed grant award to N.Y.F. F.B., supported by a fellowship grant (404527522) from the German Research Foundation (DFG)

Comments

Sasamoto, Y., Lee, C. A., Wilson, B. J., Buerger, F., Martin, G., Mishra, A., ... & Frank, N. Y. (2022). Limbal BCAM expression identifies a proliferative progenitor population capable of holoclone formation and corneal differentiation. Cell Reports, 40(6), 111166. https://doi.org/10.1016/j.celrep.2022.111166

Abstract

The corneal epithelium is renowned for high regenerative potential, which is dependent on the coordinated function of its diverse progenitor subpopulations. However, the molecular pathways governing corneal epithelial progenitor differentiation are incompletely understood. Here, we identify a highly proliferative limbal epithelial progenitor subpopulation characterized by expression of basal cell adhesion molecule (BCAM) that is capable of holocone formation and corneal epithelial sheet generation. BCAM-positive cells can be found among ABCB5-positive limbal stem cells (LSCs) as well as among ABCB5-negative limbal epithelial cell populations. Mechanistically, we show that BCAM is functionally required for cellular migration and differentiation and that its expression is regulated by the transcription factor p63. In aggregate, our study identifies limbal BCAM expression as a marker of highly proliferative corneal epithelial progenitor cells and defines the role of BCAM as a critical molecular mediator of corneal epithelial differentiation.

DOI

10.1016/j.celrep.2022.111166

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