The findings provide new insights into the role and importance of exosomes and their targeted gene transcripts, 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.
A magnification of the four distinct strata of human skin. At the top is the stratum corneum consisting of several layers of flat, dead, waterproof keratinocytes -- the outer layer of skin cells. Beneath the stratum corneum are the strata granulosum, spinosum and basale. It is in the stratum basale that resident stem cells differentiate to provide new cells and renew the skin. Below the stratum basale is the dermis, a collagen rich tissue that cushions the body.
Credit: UC San Diego School of Medicine
Stem cells, of course, 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 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 that contain errors resulting in the translation of dysfunctional proteins which could potentially be deleterious to the cell.
"In short," said George L. Sen, PhD, assistant professor of medicine and cellular and molecular medicine, "the exosome functions as a surveillance system in cells to regulate the normal turnover of RNAs as well as to destroy RNAs with errors in them."
Sen and colleagues Devendra S. Mistry, PhD, a postdoctoral research fellow, and staff scientist Yifang Chen, MD, PhD, discovered that in the epidermis the exosome functions to target and destroy mRNAs that encode for transcription factors that induce differentiation. Specifically, they found that the exosome degrades a transcription factor called GRHL3 in epidermal progenitor cells, keeping the latter undifferentiated. Upon receiving differentiation inducing signals, the progenitor cells lose expression of certain subunits of the exosome which leads to higher levels of GRHL3 protein. This increase in GRHL3 levels promotes the differentiation of the progenitor cells.
"Without a functioning exosome in progenitor cells," said Sen, "the progenitor cells prematurely differentiate due to increased levels of GRHL3 resulting in loss of epidermal tissue over time."
Sen said the findings could have particular relevance if future research determines that mutations in exosome genes are linked to skin disorders or other diseases. "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," said Sen. "This may potentially be due to loss of progenitor cells. Once mutations in 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."
Funding for this research came, in part, from the National Institutes of Health grant K01AR057828-04 and a Ray Thomas Edwards Award.
Scott LaFee | EurekAlert!
Not of Divided Mind
19.01.2017 | Hertie-Institut für klinische Hirnforschung (HIH)
CRISPR meets single-cell sequencing in new screening method
19.01.2017 | CeMM Forschungszentrum für Molekulare Medizin der Österreichischen Akademie der Wissenschaften
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
19.01.2017 | Earth Sciences
19.01.2017 | Life Sciences
19.01.2017 | Physics and Astronomy