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Does 'junk DNA' play a role in stem cell differentiation?

20 July 2020
Appeared in BioNews 1056

A part of the human genome derived from viral RNA has been shown to play a major role in inducing stem cells to become neurons.

The study, conducted by researchers at the US National Institutes of Health (NIH), focused on human endogenous retroviruses (HERV), which are segments of the human genome that originated in viruses and were incorporated into human DNA over millions of years. These retroviruses have long been considered a form of inactive 'junk DNA'. However, the researchers found that one of them is expressed at high levels by human stem cells. In particular, they found that HML-2, the envelope protein of the human endogenous retrovirus HERV-K, is expressed on the surface of stem cells and plays a major role in cell signalling.

The research, by Dr Avindra Nath, and Dr Tongguang Wang at the NIH's National Institute of Neurological Disorders and Stroke (NINDS) in Rockville, Maryland, obtained most the cells for their experiments from human blood samples. They then converted these blood cells into induced pluripotent stem cells, which can differentiate into any human cell type. Dr Wang and his colleagues noticed that the HML-2 protein was expressed on the surface of the stem cells they studied.

One of the experiments they subsequently performed involved successively exposing the stem cells to two different solutions, which caused the cells to develop into neurons. Another involved deactivating the genes encoding the HML-2 protein, which accelerated the differentiation of the stem cells into neurons. This indicates that the deactivation of the HML-2 protein enables human stem cells to become neurons during embryonic development.

In contrast, the researchers were able to interrupt the stem cells differentiating into neurons by adding an increased number of HML-2 genes to the stem cells. A final experiment uncovered that HML-2 interacted with an immune cell protein called CD98HC, which resulted in halting the stem cells differentiating into neurons. It is believed that this is due to the same chemical reactions that are also know to control cell growth and tumours.  

The results of this study point to a major developmental role for the envelope protein HML-2, found on the exterior of the human endogenous retrovirus HERV-K, which is used by the virus to invade cells. The HERV-K virus is one of many which has incorporated parts of its genome into the human genome.

These findings reinforce other recent evidence indicating that endogenous retroviruses, rather than being functionless, have significant biological functions in humans. Specifically, Dr Nath's results show that deactivation of the HML-2 gene plays a major role in the development of neurons in humans.

This research was published online in the peer-reviewed journal Proceedings of the National Academy of Sciences earlier this month.

Regulation of stem cell function and neuronal differentiation by HERV-K via mTOR pathway
PNAS |  15 July 2020
Turning off 'junk DNA' may free stem cells to become neurons
National Institutes of Health |  13 July 2020
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