Identification of BST2 as a conjunctival epithelial stem/progenitor cell marker

Masahiro Kitao; Ryuhei Hayashi; Kimihito Nomi; Reiko Kobayashi; Tomohiko Katayama; Hiroshi Takayanagi; Akiko Oguchi; Yasuhiro Murakawa; Kohji Nishida

doi:10.1016/j.isci.2023.107016

Identification of BST2 as a conjunctival epithelial stem/progenitor cell marker

iScience. 2023 Jun 5;26(7):107016. doi: 10.1016/j.isci.2023.107016. eCollection 2023 Jul 21.

Authors

Masahiro Kitao¹, Ryuhei Hayashi^{1

2

3}, Kimihito Nomi⁴, Reiko Kobayashi¹, Tomohiko Katayama¹, Hiroshi Takayanagi^{1

2}, Akiko Oguchi⁵, Yasuhiro Murakawa^{5

6}, Kohji Nishida^{1

3

7}

Affiliations

¹ Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
² Department of Stem Cells and Applied Medicine, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
³ Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Suita, Osaka 565-0871, Japan.
⁴ Business Strategy Office, ROHTO Pharmaceutical, Osaka, Osaka 544-0012, Japan.
⁵ RIKEN-IFOM Joint Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan.
⁶ Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto, Kyoto 606-8501, Japan.
⁷ Premium Research Institute for Human Metaverse Medicine (WPI-PRIMe), Osaka University, Suita, Osaka 565-0871, Japan.

Abstract

The conjunctival epithelium consists of conjunctival epithelial cells and goblet cells derived from conjunctival epithelial stem/progenitor cells. However, the source of these cells is not well known because no specific markers for conjunctival epithelial stem/progenitor cells have been discovered. Therefore, to identify conjunctival epithelial stem/progenitor cell markers, we performed single-cell RNA sequencing of a conjunctival epithelial cell population derived from human-induced pluripotent stem cells (hiPSCs). The following conjunctival epithelial markers were identified: BST2, SLC2A3, AGR2, TMEM54, OLR1, and TRIM29. Notably, BST2 was strongly positive in the basal conjunctival epithelium, which is thought to be rich in stem/progenitor cells. Moreover, BST2 was able to sort conjunctival epithelial stem/progenitor cells from hiPSC-derived ocular surface epithelial cell populations. BST2-positive cells were highly proliferative and capable of successfully generating conjunctival epithelial sheets containing goblet cells. In conclusion, BST2 has been identified as a specific marker of conjunctival epithelial stem/progenitor cells.

Keywords: Cell biology; Stem cells research; Transcriptomics.