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Key mechanism for skin cell renewal identified

Early molecular switch inside nucleus is crucial for deciding fate of skin stem cells.

DIRTT Life Sciences
Image by: DIRTT
Image by: DIRTT

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Scientists have identified a key mechanism controlling skin regeneration. This is based on an early molecular switch located inside a nucleus that is crucial for deciding fate of skin stem cells. The stem cells in epithelial tissues continuously make fate decisions between self-renewal and differentiation.

By being table to identify and tap into the switch that leads to either outcome holds the key to skin regeneration. Through this, it is hoped that the new findings will aid medical understanding of cancer and wound healing.

The outer layer of skin, the epidermis, continuously turns over to replace dead or damaged cells throughout our lifetime. This outer layer of the skin provides an essential barrier for the human body, reducing water loss and combating environmental threats. This process involves significant changes from more than 6,000 genes, ceasing stem cell proliferation while activating barrier-function genes.

What scientists from Northwestern University have been seeking is understanding what the molecular mechanisms for controlling skin epidermal regeneration are.  The answer is a molecular switch, controlled through a protein called cyclin-dependent kinase 9 (CDK9).

This switch plays an early and critical role in the skin stem cell differentiation process. This switch is “off” in the stem cells. When the switch is turned on, a specific group of genes is activated, and this triggers downstream gene regulators. This allows the skin cells to progressively gain barrier function.

Specifically a kinase activity switch of the protein CDK9 plays a key role in the decision of cells to initiate differentiation and progressively acquire the barrier function of the tissue. CDK9 plays crucial roles in modulating gene expression at the step of “transcription,” a process of copying specific DNA regions to RNA, before RNA can serve as templates for synthesizing new proteins.

According to lead researcher Xiaomin Bao: “Skin stem cells need to continuously make decisions, to either make more copies of themselves — a process known as self-renewal — or to switch their fate towards differentiation. A delicate balance between these two decisions is crucial to maintain the integrity of skin and its barrier function.”

Through the discovery the researchers have also determined that the switch is bound to selected genomic regions inside the stem cells, standing ready to trigger the cell fate switch of initiating the stem cell’s movement towards differentiation.

The findings are published in the journal Nature Communications. The research paper is titled “CDK9 activity switch associated with AFF1 and HEXIM1 controls differentiation initiation from epidermal progenitors.”

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Dr. Tim Sandle is Digital Journal's Editor-at-Large for science news. Tim specializes in science, technology, environmental, business, and health journalism. He is additionally a practising microbiologist; and an author. He is also interested in history, politics and current affairs.

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