In a groundbreaking study, researchers at the Children's Medical Centre Research Institute (CRI) at UT Southwestern discovered that ancient viral remnants within the human genome, previously thought to be "junk DNA," play an important role in increasing blood cell production during pregnancy and after significant blood loss. Published in Science, this study offers new perspectives on the function of retrotransposons, ancient viral sequences rooted in the human genome.

The main authors of the study, Dr. Sean J. Morrison, Director of CRI, and Dr. Julia Phan, sought to understand how pregnancy or bleeding activated blood-forming stem cells, which typically divide infrequently. The reseaThe researchers analyzed stem cells from both pregnant and non-pregnant mice and found that the pregnant mouse's stem cells activated retrotransposons. osite of what we expected," Dr. Morrison explained. "If there's ever a time to protect the integrity of the genome and avoid mutations, it would be during pregnancy." 

Because they do not encode proteins involved in cellular function, retrotransposons, sometimes known as "junk DNA," replicate using an enzyme similar to the HIV virus. While humans have evolved ways to keep retrotransposons inactive due to their ability to break DNA, the study discovered that the retrotransposons may have an adaptive utility, particularly during pregnancy. 

The researchers used medicines that inhibit reverse transcriptase, commonly used to limit HIV replication, to stop retrotransposons in mice. Surprisingly, whereas these medications had no effect on blood cell synthesis in non-pregnant mice, they caused anemia in pregnant mice by inhibiting the rise of blood-forming stem cells. The study concludes that retrotransposons play an important role in preventing anemia during pregnancy.

Further research revealed that immunological sensors called cGAS and STING identify retrotransposons and trigger a modest interferon response. This response, rather than damaging stem cells, stimulates blood cell synthesis. "We initially believed that the immune system might kill the stem cells due to interferon, but we discovered that the retrotransposons activated just enough interferon to stimulate blood cell production," said Phan, the doctor.

Dr. Phan and Dr. Morrison did not limit their investigation to mice. Blood samples from pregnant women, including three who were on reverse transcriptase inhibitors, revealed similar activation of retrotransposons and interferons. Dr. Alpaslan Tasdogan, a collaborator from University Hospital Essen in Germany, corroborated these findings in humans. Dr. Tasdogan said, "These insights help us understand some of the underlying mechanisms that contribute to anaemia during pregnancy," and he plans to conduct clinical research to investigate these processes in patients.

This study builds on previous discoveries from the Morrison Lab, which showed that estrogen plays a role in stem cell activation during pregnancy. "This work changes the way we think about mechanisms that regulate tissue regeneration," Dr. Morrison stated. "We speculate other kinds of stem cells may also co-opt retrotransposons and immune sensors during tissue regeneration." 

The work highlights the developing understanding of "junk DNA" and its possible role in human biology.