Vitamin A could have a key role in both stem cell biology and wound healing: Study

Lineage plasticity, observed in various tissues in response to injury and in cancer, is best studied in minor skin injuries due to the skin's constant exposure to damage. When scratches or abrasions damage the epidermis, hair follicle stem cells are the first to respond, with other skin stem cells following suit to regenerate the skin. Some stem cells, originally dedicated to hair growth, transition into epidermal stem cells to aid in repair. This transition involves temporary expression of transcription factors from both hair and epidermal stem cells.

“Our goal was to understand this state well enough to learn how to dial it up or down,” said Elaine Fuchs professor at Rockefeller University. “We now have a better understanding of skin and hair disorders, as well as a path toward preventing lineage plasticity from contributing to tumor growth.”

The researchers explored lineage plasticity, highlighting its dual role: crucial for directing stem cells to areas needing repair, yet potentially leading to prolonged repair states and certain cancers if uncontrolled. To understand the mechanism, they screened small molecules in cultured mouse hair follicle stem cells, mimicking wound conditions were surprised to find that retinoic acid, the active form of vitamin A, was essential for these stem cells to exit lineage plasticity and differentiate into hair or epidermal cells in vitro.

“Through our studies, first in vitro and then in vivo, we discovered a previously unknown function for vitamin A, a molecule that has long been known to have potent but often puzzling effects on skin and many other organs,” said Fuchs.

The findings revealed that genetic, dietary, and topical interventions boosted or removed retinoic acid from mice and confirmed its role in balancing how stem cells respond to skin injuries and hair regrowth. Retinoids did not operate on their own: their interplay with signalling molecules such as BMP and WNT influenced whether the stem cells should maintain quiescence or actively engage in regrowing hair.

“By defining the minimal requirements needed to form mature hair cell types from stem cells outside the body, this work has the potential to transform the way we approach the study of hair biology,” said Matthew Tierney, lead author of the paper.

Reference: MATTHEW T. TIERNEY, LISA POLAK, YIHAO YANG, MERVE DENIZ ABDUSSELAMOGLU, INWHA BAEK, KATHERINE S. STEWART, AND ELAINE FUCHS; Journal: Science; DOI: 10.1126/science.adi7342