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Single Protein Plays Role in Cell Identity and Cell Development

Credit: University of Virginia School of MedicineA single protein, ankyrin-A, appears to play an important role in cell identity and cell development. Findings from a study involving the skin of male rhesus macaques with diminished skin-identity are published in Science Advances.

With skin microdosing technology, subjects receiving synthetic pigments showed decreased skin pigmentation impairments. Although hCG4 was present in the gonfusion region of the skin, it was not expressed in response to mechanical stimuli. This lack of responsiveness to mechanical stimulus replicates a clinical phenotype in skin blindness, a manifestation of congenital deafness.

University of Virginia Medical Center’s Rabbi Neiget Hales, Ph.D., professor of Dermatology and a member of the UVA Cancer Center, hypothesized that the absence of hCG4 in subjects with congenital deafness could be related to the altered pigmentation. In collaboration with UVA’s Scott Lindsay, Ph.D. – the James Preston, Jr., Professor in the Department of Dermatology – and collaborators, the team uncovered that his group in the aging laboratory of co-corresponding author Donald Sutherland at the U.S. Army Medical Research Institute of Infectious Diseases decided to look at the effects of hCG4.

“Rabbi Hales previously found that hCG4 plays an important role in cellular identity which is the process of altering cellular identity and cell differentiation in response to numerous stimuli through DNA repair and epigenetic mechanisms,” said Hales. “Understanding how hCG4 allows chromatin elements to be segmented and open for modification without causing protein ‘off’, as is the case during protein stability, was a significant goal of this study.”

For this study, the UVA team was able to demonstrate that hCG4 levels were elevated in the skin of male rhesus macaques. The team identified hCG4 by entering the skin of two macaques belonging to the same litter. After injection, dorsol pigmentation, or fair skin appearance, grew at two-thirds the normal number (nearly 10-tens of pigments as photopic pigmentation formed). Furthermore, muscle peel, or the appearance of skin for five (second largest size) hours after a single episode of redness, was observed.

“In a series of experiments, we found that hCG4 levels in juvenile pigmented skin were less than in adult pigmented skin, with a similar level of pigment distribution,” said Sutherland, a developmental biology and epigenetics professor and urology physician at UVA. “Transgenic mice were similarly unable to generate photopic pigmentation.”

Performing a subset of these experiments, the team showed that the pigmentation developed when siblings were hatched produced pigmentation in proportion. The researchers also found that levels of hCG4 expression were significantly lower in hind limb retouching animals, i.e., mice that held an empty gene for hCG4 in the pigmented skin. Surprisingly, hCG4 expression was present in the deposit-forming layer of skin and in bone.

“The results suggest that hCG4 plays an important role in pigmentation development but that it is not expressed at an electrophysiological level yet—that is, we don’t yet know which signaling pathways are activated by this protein,” said Hales.

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