Discovered two limbal stem cell populations that control corneal homeostasis and wound healing processes

Ruby Shalom-Feuerstein, Anna Altshuler and Aya Amitai-Lange, the workforce of Brighter project at Technion, Israel, led a work that has just been published in the prestigious journal Cell Stem Cell. They describe for the first time the existence of two limbal stem cell populations that have different characteristics and functions in the maintenance of the cornea. This pioneering study opens the doors to the development of accurate treatments for corneal disorders.

Limbal epithelial stem cells (LSCs) are responsible for the renewal of the cornea and up to date, have been seen by the scientific community as rare and slow-cycling cells. Now, a team or researchers from different laboratories at Technion – Israel Institute of Technology have discovered that in fact, the LSCs are composed by two different populations of cells, with distinct characteristics and niches: the quiescent and the active limbal stem cells. The work, led by Ruby Shalom-Feuerstein and signed by Anna Altshuler and Aya Amitai-Lange as first authors, has been recently published in the journal Cell Stem Cell. As experts in the epithelial stem cells field, these researchers from the Laboratory of Epithelial Stem Cells & Pathophysiology at Technion, are in charge to provide the cellular models and scientific knowledge about stem cell biology to BRIGHTER Project and to collaborate on the fabrication and testing of the new skin engineered tissues using the biomaterial scaffolds developed by the bioengineering partners.


The limbus is a ring-shaped zone at the corneal-conjunctival boundary that hosts the corneal epithelial stem cells, that is, the cells responsible for the renewal of old corneal cells and of wound healing response. Thus, a region extremely important for the proper functioning of the eyes.



Combining single cell RNA sequencing and quantitative lineage tracing techniques in mouse, researchers discovered the existence of two populations of abundant limbal epithelial stem cells (LSCs) localized in separate and well-defined sub-compartments, termed the ‘‘outer’’ and ‘‘inner’’ limbus. The quiescent LSCs (qLSCs) are found in the outer limbus zone, co-localize with and regulated by T-cells. qLSCs participate in wound healing and boundary formation. On the other hand, the active LSCs (aLSCs) that reside in the inner limbus are responsible for the cornea homeostasis and renewal.

The observation that there are two populations of stem cells, and that these cells are abundant, challenges the convectional LSC dogma, that considered a single rare LSC population. Nevertheless, this conclusion fits with the equipotent stem cell model, describing epithelial stem cell dynamics in the gut, epidermis and the oesophagus.

The complete atlas of the murine corneal epithelial lineage presented in this work represents a highly valuable tool to understand eyes disorders and help finding preventive and curative treatments for patients that suffer from corneal blindness due to LSC deficiency. In summary, the new data provided in this study pave the way to the development accurate bioengineering tools, as high-quality organoids, better LSC-based therapies, and application of LSCs in regenerative medicine.


Reference article: 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 and Ruby Shalom-Feuerstein. Cell Stem Cell 28, 1–14, 2021.