Exosome are Key Proteins to Self-Renewing Skin
Our skin epidermal and stem cells, avoid premature differentiation, preserving their ability to produce new skin cells throughout our lives
New research provides insights into the role and importance of exosomes, and may help point the way to new drugs or therapies for not just skin diseases, but other disorders in which stem and progenitor cell populations are affected.
Researchers at the University of California, San Diego School of Medicine published their findings in the July 6 issue of Cell Stem Cell.
Stem cells, are specialized cells
capable of endlessly replicating
to become any type of cell needed,
a process known as differentiation.
Progenitor cells are more limited,
typically differentiating into a specific type of cell
and able to divide only a fixed number of times.
Throughout life, human skin self-renews. Progenitor and stem cells deep in the epidermis constantly produce new skin cells called keratinocytes that gradually rise to the skin's surface where they will be sloughed off.
One of the ways that stem and progenitor cells maintain internal health during their lives is through the exosome a collection of approximately 11 proteins responsible for degrading and recycling different RNA elements, such as messenger RNA, that wear out or develop errors resulting in dysfunctional proteins, potentially dangerous to the cell.
"In short, the exosome functions as a surveillance system
in cells to regulate normal turnover of RNAs
as well as to destroy error ridden RNAs."
George L. Sen, PhD
Sen and colleagues discovered that in the epidermis the exosome targets and destroys mRNAs that induce differentiation. Specifically, they found that the exosome desolves a protein called GRHL3 found in the epidermal progenitor cells.
After receiving signals to induce differentiation, the progenitor cells lose certain subunits of the exosome which leads to higher levels of GRHL3. This increase in GRHL3 promotes differentiation of the progenitor cells.
Sen: "Without a functioning exosome, the progenitor cells prematurely differentiate due to increased levels of GRHL3 which results in loss of epidermal tissue over time."
Sen said the findings could have particular relevance if future research determines which mutations in exosome genes are linked to skin disorders or other diseases.
Sen: "Recently there was a study showing that recessive mutations in a subunit of the exosome complex can lead to pontocerebellar hypoplasia, a rare neurological disorder characterized by impaired development or atrophy of parts of the brain. This may potentially be the result of loss of progenitor cells.
Once mutations in the exosome complex genes are identified in either skin diseases or other diseases like pontocerebellar hypoplasia, it may be possible to design drugs targeting these defects."
Devendra S. Mistry, PhD, a postdoctoral research fellow, and staff scientist Yifang Chen, MD, PhD collaborated with Dr. Sen in this research project.
Funding for this research came, in part, from the National Institutes of Health grant K01AR057828-04 and a Ray Thomas Edwards Award.