Discrete limbal epithelial stem cell populations mediate corneal homeostasis and wound healing

Anna Altshuler, Aya Amitai-Lange, Noam Tarazi, Sunanda Dey, Lior Strinkovsky, Shira Hadad-Porat, Swarnabh Bhattacharya, Waseem Nasser, Jusuf Imeri, Gil Ben-David, Ghada Abboud-Jarrous, Beatrice Tiosano, Eran Berkowitz, Nathan Karin, Yonatan Savir, Ruby Shalom-Feuerstein

Research output: Contribution to journalArticlepeer-review

Abstract

The accessibility and transparency of the cornea permit robust stem cell labeling and in vivo cell fate mapping. Limbal epithelial stem cells (LSCs) that renew the cornea are traditionally viewed as rare, slow-cycling cells that follow deterministic rules dictating their self-renewal or differentiation. Here, we combined single-cell RNA sequencing and advanced quantitative lineage tracing for in-depth analysis of the murine limbal epithelium. These analysis revealed the co-existence of two LSC populations localized in separate and well-defined sub-compartments, termed the “outer” and “inner” limbus. The primitive population of quiescent outer LSCs participates in wound healing and boundary formation, and these cells are regulated by T cells, which serve as a niche. In contrast, the inner peri-corneal limbus hosts active LSCs that maintain corneal epithelial homeostasis. Quantitative analyses suggest that LSC populations are abundant, following stochastic rules and neutral drift dynamics. Together these results demonstrate that discrete LSC populations mediate corneal homeostasis and regeneration.

Original languageEnglish
Pages (from-to)1248-1261.e8
JournalCell Stem Cell
Volume28
Issue number7
DOIs
StatePublished - 1 Jul 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2021 Elsevier Inc.

Keywords

  • cornea
  • immune cells
  • limbal stem cells
  • limbus
  • lineage tracing
  • mathematical modeling
  • niche
  • single cell RNA sequencing
  • stem cell dynamics

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

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