The key (proteins) to self-renewing skin

July 5, 2012, University of California - San Diego
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

In the July 6 issue of Cell Stem Cell, researchers at the University of California, San Diego School of Medicine describe how human epidermal progenitor cells and stem cells control transcription factors to avoid premature differentiation, preserving their ability to produce new skin cells throughout life.

The findings provide new insights into the role and importance of exosomes and their targeted gene transcripts, and may help point the way to or therapies for not just , but other disorders in which stem and progenitor are affected.

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, self-renews. Progenitor and deep in the epidermis constantly produce new 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 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 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 . 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."

Explore further: Restoring what's lost: Uncovering how liver tissue regenerates

Related Stories

Restoring what's lost: Uncovering how liver tissue regenerates

March 12, 2012
The liver is unique among mammalian organs in its ability to regenerate after significant tissue damage or even partial surgical removal.

A shot of young stem cells made rapidly aging mice live longer and healthier

January 3, 2012
Mice bred to age too quickly seemed to have sipped from the fountain of youth after scientists at the University of Pittsburgh School of Medicine injected them with stem cell-like progenitor cells derived from the muscle ...

Recommended for you

More surprises about blood development—and a possible lead for making lymphocytes

January 22, 2018
Hematopoietic stem cells (HSCs) have long been regarded as the granddaddy of all blood cells. After we are born, these multipotent cells give rise to all our cell lineages: lymphoid, myeloid and erythroid cells. Hematologists ...

How metal scaffolds enhance the bone healing process

January 22, 2018
A new study shows how mechanically optimized constructs known as titanium-mesh scaffolds can optimize bone regeneration. The induction of bone regeneration is of importance when treating large bone defects. As demonstrated ...

Bioengineered soft microfibers improve T-cell production

January 18, 2018
T cells play a key role in the body's immune response against pathogens. As a new class of therapeutic approaches, T cells are being harnessed to fight cancer, promising more precise, longer-lasting mitigation than traditional, ...

Weight flux alters molecular profile, study finds

January 17, 2018
The human body undergoes dramatic changes during even short periods of weight gain and loss, according to a study led by researchers at the Stanford University School of Medicine.

Secrets of longevity protein revealed in new study

January 17, 2018
Named after the Greek goddess who spun the thread of life, Klotho proteins play an important role in the regulation of longevity and metabolism. In a recent Yale-led study, researchers revealed the three-dimensional structure ...

The HLF gene protects blood stem cells by maintaining them in a resting state

January 17, 2018
The HLF gene is necessary for maintaining blood stem cells in a resting state, which is crucial for ensuring normal blood production. This has been shown by a new research study from Lund University in Sweden published in ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.