# Identify mechanisms of dedifferentiation during limbal stem cell niche reconstruction.

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $159,275

## Abstract

Project Summary
The corneal limbal stem cells (LSC) play a vital function in homeostasis and wound healing.
Damage to the LSC and other pathologies associated LSC deficiency (LSCD) cause cornea
neovascularization, corneal opacification, and vision loss. Current treatment paradigm is based
on the transplantation of LSC into patients to restore the LSC niche. Substantial effort over the
last few years aims at identifying sources of LSC for transplantation with varying degree of
success. However, our recent work indicates that transplantation of LSC might not be the the
only useful treatment paradigm for LSCD. We showed that committed epithelial cells that have
lost the stem cell marker K15 are able to dedifferentiate and repopulate the stem cell niche. If
this process can be controlled and manipulated it could provide alternative treatment that can
avoid the need for complex stem cell transplantation. We have shown that the niche is important
for the process of dedifferentiation demonstrating that dedifferentiation and repopulation of the
niche require communication between cells that remain in the niche and corneal epithelial cells.
Here we will use cutting edge long term multi-day imaging of corneal organ culture to investigate
both sides of the communication between the niche and epithelial cells. In Aim #1 we will take a
pharmacological approach and screen 99 different compounds and acquire long timelapse
movies of the restoration of the LSC niche in the presence of different drugs. The high content
analysis will provide key information on the different signaling pathways used by the niche to
recruit and induce the dedifferentiation of epithelial cells. In Aim #2 we will focus on the receiver
side of the communication and analyze the source of cells used to repopulate the niche. Using
advanced light sheet microscopy approaches we will track individual cells and discover the
identity of the cells that are capable of dedifferentiation. Single cell tracking will show whether
the ability to dedifferentiate is ubiquitous or whether only a small subset of cells maintain the
ability to dedifferentiate. The successful completion of these aims will provide key insights into
the physiological process of LSC niche recovery and will pave the way to the development of
new treatments to LSCD.

## Key facts

- **NIH application ID:** 9902499
- **Project number:** 5R21EY030250-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Roy Wollman
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $159,275
- **Award type:** 5
- **Project period:** 2019-04-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9902499

## Citation

> US National Institutes of Health, RePORTER application 9902499, Identify mechanisms of dedifferentiation during limbal stem cell niche reconstruction. (5R21EY030250-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9902499. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*