The mechanisms that ensure developmental progression in the early human embryo remain largely unknown. A new study suggests that ‘selfish DNA,’ or transposons, controls early human development.
As reported by Sinai Health researchers, these transposons can move around the genome.
People often see transposons like viruses that invade our cells just to make copies of themselves. However, we’ve found that these elements are essential for early development, not just selfish parasites.
The study shows that transposable elements, especially LINE-1, are crucial for normal early development of human embryos. While our genes comprise less than 2% of our genome, LINE-1 elements account for about 20%. These elements can move and copy themselves, leading to the idea that they’re “selfish DNA” because they can disrupt normal genes.
Scientists used to think these elements mainly were harmful and could cause diseases like hemophilia and cancer. However, Dr. Juan Zhang, a senior co-author and postdoctoral fellow, found it interesting that LINE-1 RNA is very active in early embryos, suggesting these elements play an essential role during this critical time.
Dr. Zhang said, “If transposons are bad and dangerous, why do we see them active in the early embryo? This is an embryo that’s just beginning its formation. Any dangerous insertion into the genome at this point will propagate throughout the rest of the individual’s development.”
When Dr. Zhang blocked LINE-1 activity in human embryonic stem cells, the cells reverted to a very early stage called the 8-cell stage, where all cells are identical and can become both the embryo and the placenta. As stem cells develop further, they can still form fetal cells but become less able to contribute to the placenta, which is vital for the mother’s nutrient supply.
Further research revealed that LINE-1 RNA helps organize DNA within the cell’s nucleus. It plays a crucial role in moving chromosome 19, which contains essential genes for the 8-cell stage, to a specific area of the nucleus that silences certain genes. This organization helps ensure the embryo can continue to develop appropriately.
Dr. Zhang said, “We show that LINE-1 regulates gene expression at a crucial turning point where the embryo starts to specialize its cells for various functions. Our results indicate that this is not an accidental but a vital evolutionary mechanism.”
Surprisingly, LINE-1 elements are not just jumping around and causing harmful mutations; they play a crucial role in helping early human development progress smoothly. This discovery highlights their importance during the early stages of growth.
The findings could significantly impact fertility treatments and stem cell research for regenerative medicine. They also open new avenues to explore LINE-1’s roles in diseases like neurological disorders and cancer.
Dr. Anne-Claude Gingras praised the research, noting that there’s still much to learn about human development and these mysterious genetic elements. She congratulated the team for their groundbreaking insights into human biology and looked forward to further discoveries.
Journal Reference:
- Juan Zhang, Lamisa Ataei, et al. LINE1 and PRC2 control nucleolar organization and repression of the 8C state in human ESCs. Developmental Cell. DOI: 10.1016/j.devcel.2024.09.024
