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Updated: Jul 4, 2026

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The human limbus functions as an instructive epithelial transition zone.

Natasha Frank1, Yuzuru Sasamoto2, Yoshiko Fukuda3

  • 1Brigham and Women's Hospital.

Research Square
|July 3, 2026
PubMed
Summary

The adult human limbus is not a rigid barrier but an instructive zone. Limbal stem cells are bipotent, guided by growth factors like KGF and EGF to adopt corneal or conjunctival fates.

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Area of Science:

  • Ophthalmology
  • Stem Cell Biology
  • Epithelial Biology

Background:

  • The limbus was traditionally viewed as a barrier enforcing corneal identity via limbal stem cells.
  • Conjunctivalization of the cornea was considered a failure of this lineage barrier.

Purpose of the Study:

  • To investigate the functional role of the adult human limbus in epithelial cell fate determination.
  • To redefine the boundary and mechanisms governing corneal and conjunctival epithelial identity.

Main Methods:

  • Integrated single-cell transcriptomics and spatial mapping of the limbus.
  • Clonal functional analysis of limbal basal progenitors.
  • Mechanistic studies involving keratinocyte growth factor (KGF) and epidermal growth factor (EGF).

Main Results:

  • The limbus acts as a dynamic epithelial transition zone, not a rigid boundary.
  • Limbal basal progenitors are intrinsically bipotent, capable of forming corneal or conjunctival epithelium.
  • KGF and EGF act as molecular switches, with KGF promoting corneal fate (via PAX6/MYC) and EGF sustaining conjunctival identity.

Conclusions:

  • The adult human limbus is a fate-determining niche that instructs epithelial identity.
  • Epithelial identity in adult human tissues remains plastic and instructable.
  • Growth factor signaling (KGF/EGF) is crucial for maintaining the conjunctival-corneal interface homeostasis.