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

Sci Rep. 2019 Jul 17;9(1):10373. doi: 10.1038/s41598-019-46793-6.

Abstract

Notch signaling has been shown to regulate the homeostasis and wound healing of the corneal epithelium. We investigated the effect of Notch inhibition in the human limbal stem/progenitor cells (LSCs) in vitro by using small molecules. Treatment of the LSCs with DAPT and SAHM1 reduced the proliferation rate and maintained the undifferentiated state of the LSCs in a concentration dependent manner. Stratification and differentiation of the corneal epithelium were not reduced after Notch inhibition, indicating that the function of the corneal basal cells is retained. Our findings suggest that Notch signaling plays a role in the proliferation and maintenance of LSCs.

Publication types

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

MeSH terms

  • Adult
  • Adult Stem Cells / cytology
  • Adult Stem Cells / drug effects*
  • Adult Stem Cells / metabolism
  • Aged
  • Basic Helix-Loop-Helix Transcription Factors / biosynthesis
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Cell Cycle Proteins / biosynthesis
  • Cell Cycle Proteins / genetics
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Diamines / pharmacology
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Humans
  • Limbus Corneae / cytology*
  • Middle Aged
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Receptor, Notch1 / antagonists & inhibitors
  • Receptor, Notch1 / biosynthesis
  • Receptor, Notch1 / genetics
  • Receptor, Notch1 / physiology*
  • Receptor, Notch2 / antagonists & inhibitors
  • Receptor, Notch2 / biosynthesis
  • Receptor, Notch2 / genetics
  • Receptor, Notch2 / physiology*
  • Thiazoles / pharmacology
  • Transcription Factor HES-1 / biosynthesis
  • Transcription Factor HES-1 / genetics
  • Young Adult

Substances

  • 24-diamino-5-phenylthiazole
  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Cycle Proteins
  • Diamines
  • HEY1 protein, human
  • NOTCH1 protein, human
  • NOTCH2 protein, human
  • RNA, Messenger
  • Receptor, Notch1
  • Receptor, Notch2
  • Thiazoles
  • Transcription Factor HES-1
  • HES1 protein, human