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

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; Natasha Y Frank

doi:10.1016/j.celrep.2022.111166

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

Cell Rep. 2022 Aug 9;40(6):111166. doi: 10.1016/j.celrep.2022.111166.

Authors

Yuzuru Sasamoto¹, Catherine A A Lee¹, Brian J Wilson², Florian Buerger³, Gabrielle Martin¹, Ananda Mishra¹, Shoko Kiritoshi⁴, Johnathan Tran⁵, Gabriel Gonzalez⁶, Friedhelm Hildebrandt³, Vickie Y Jo⁷, Christine G Lian⁷, George F Murphy⁷, Bruce R Ksander⁸, Markus H Frank⁹, Natasha Y Frank¹⁰

Affiliations

¹ Division of Genetics, Brigham and Women's Hospital, Boston, MA, USA; Transplant Research Program, Boston Children's Hospital, Boston, MA, USA.
² Transplant Research Program, Boston Children's Hospital, Boston, MA, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.
³ Department of Nephrology, Boston Children's Hospital, Boston, MA, USA.
⁴ Division of Genetics, Brigham and Women's Hospital, Boston, MA, USA.
⁵ Transplant Research Program, Boston Children's Hospital, Boston, MA, USA.
⁶ Division of Genetics, Brigham and Women's Hospital, Boston, MA, USA; Department of Medicine, VA Boston Healthcare System, Boston, MA, USA.
⁷ Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
⁸ Massachusetts Eye and Ear Infirmary, Schepens Eye Research Institute, Boston, MA, USA.
⁹ Transplant Research Program, Boston Children's Hospital, Boston, MA, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA; Harvard Skin Disease Research Center, Department of Dermatology, Brigham and Women's Hospital, Boston, MA, USA; School of Medical and Health Sciences, Edith Cowan University, Perth, WA, Australia. Electronic address: markus.frank@childrens.harvard.edu.
¹⁰ Division of Genetics, Brigham and Women's Hospital, Boston, MA, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA; Department of Medicine, VA Boston Healthcare System, Boston, MA, USA. Electronic address: nyfrank@bwh.harvard.edu.

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.

Keywords: ABCB5; BCAM; CP: Stem cell research; adhesion; heterogeneity; laminin α5; limbal stem cell deficiency; limbal stem cells; migration; proliferation; single-cell RNA-seq; transit-amplifying cells.

Published by Elsevier Inc.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Cell Differentiation
Cells, Cultured
Cornea
Epithelial Cells / metabolism
Epithelium, Corneal*
Limbus Corneae* / metabolism
Stem Cells / metabolism

Abstract

Publication types

MeSH terms

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