Notch Inhibition Prevents Differentiation of Human Limbal Stem/Progenitor Cells in vitro

Sheyla González1, Heui Uhm2, Sophie X Deng3

  • 1Cornea Division, Stein Eye Institute, University of California, Los Angeles, CA, 90095, USA.

Scientific Reports
|July 19, 2019
PubMed

Insights

Notch inhibition reduces human limbal stem/progenitor cell proliferation while maintaining their undifferentiated state. This suggests Notch signaling is crucial for LSC maintenance and proliferation in corneal epithelium homeostasis.

Area of Science:

  • Ophthalmology
  • Stem Cell Biology
  • Molecular Biology

Background:

  • Notch signaling regulates corneal epithelium homeostasis and wound healing.
  • Human limbal stem/progenitor cells (LSCs) are critical for maintaining corneal transparency.

Purpose of the Study:

  • To investigate the role of Notch signaling in regulating human limbal stem/progenitor cells (LSCs).
  • To determine the effect of Notch inhibition on LSC proliferation and differentiation in vitro.

Main Methods:

  • In vitro culture of human limbal stem/progenitor cells (LSCs).
  • Treatment with Notch inhibitors (DAPT and SAHM1) at varying concentrations.
  • Assessment of cell proliferation, undifferentiated state, stratification, and differentiation.

Main Results:

  • Notch inhibition by DAPT and SAHM1 reduced LSC proliferation in a dose-dependent manner.
  • Notch inhibition maintained the undifferentiated state of LSCs.
  • Corneal epithelium stratification and differentiation were not impaired by Notch inhibition.

Conclusions:

  • Notch signaling plays a significant role in regulating the proliferation and maintenance of LSCs.
  • Inhibiting Notch signaling can preserve the stem cell pool without compromising corneal epithelial function.

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