Additional piece: The Complexity of Early Human Embryonic Development
Introduction:
The study published in PLOS Biology sheds light on the fascinating and complex process of early human embryonic development. While we have always assumed that the development of the embryo follows a linear path, the findings from this research challenge our long-held assumptions. They reveal the existence of an overlooked cell type that self-destructs within days of forming, acting as a quality control mechanism to protect the developing fetus. This discovery not only deepens our understanding of what happens in the crucial early stages of life after fertilization but also holds potential implications for improving IVF and regenerative medicine treatments.
Unveiling the Intricate Journey:
Each adult human body comprises trillions of cells, but it all begins with a single fertilized egg. This fertilized egg undergoes rapid cell divisions, multiplying and differentiating to give rise to various cell types that ultimately form the placenta and the embryo. However, the recent study reveals that around a quarter of the cells from 5-day-old embryos do not fit into any known cell type category such as preembryo or preplacenta. Upon further investigation, scientists identified these cells as carrying “young transposable elements” or “jumping genes,” which have the ability to copy themselves and integrate into DNA, often causing damage in the process.
Quality Control through Self-Destruction:
The presence of these jumping genes in a subset of cells points towards a quality control process at play. These damaged cells with DNA damage undergo programmed cell death, preventing them from becoming part of the developing baby. Dr. Zsuzsanna Izsvák, co-lead author of the study, explains that while humans, like all organisms, try to suppress these jumping genes, they are still active in some early developmental cells. It appears that our genetic defenses may not activate quickly enough to counter these potentially harmful genetic components. The self-destruction of damaged cells represents a survival of the fittest scenario within nearly identical cells, an intriguing concept that challenges our conventional understanding of natural selection.
The Role of Endogenous Human H Virus:
Intriguingly, the researchers found that the key cells that will give rise to the embryo, known as the inner cell mass (ICM), do not contain jumping genes. Instead, these cells express a virus-like gene called endogenous human H virus, which helps suppress the activity of young jumping genes. This discovery supports the emerging pattern that humans utilize old genetic enemies to combat new ones. The intricate interplay between genes and the way they interact during early embryonic development adds another layer of complexity to the already fascinating subject.
Implications for IVF and Regenerative Medicine:
Understanding the complex processes that occur during early human embryonic development has significant implications for IVF and regenerative medicine. In the case of IVF, being able to identify and remove damaged cells that harbor jumping genes could improve the success rates of assisted reproductive technologies. The removal of such cells would ensure the selection of healthier cells, increasing the chances of a successful pregnancy. Additionally, in the field of regenerative medicine, where researchers aim to harness the potential of stem cells for tissue repair and regeneration, this newfound understanding of quality control mechanisms within the early embryo could contribute to more efficient and safer treatments.
Summary:
The recent study on early human embryonic development offers insights into a previously overlooked cell type that self-destructs within days of formation. These cells, containing jumping genes, undergo programmed cell death due to DNA damage, acting as a quality control mechanism to protect the developing fetus. This discovery challenges our assumptions about the sequential nature of early embryonic development and sheds light on the interplay between different cell types. The presence of endogenous human H virus in cells destined to become the embryo highlights the strategic use of old genetic enemies to combat potentially harmful genetic components. The findings have important implications for improving IVF outcomes and advancing regenerative medicine. By further unraveling the complexities of early human embryonic development, scientists pave the way for new breakthroughs and advancements in reproductive and regenerative healthcare.
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Scientists studying gene activity data from the early human embryo have discovered an overlooked cell type that self-destructs within days of forming, as part of a quality control process to protect the developing fetus. The findings provide insight into what happens early in life after fertilization, which could help improve IVF or regenerative medicine treatments in the future.
A new study published on June 20, 2023 in PLOS Biology by an international team of scientists, including researchers from the University of Bath, finds that our earliest development in the womb may be quite different from what we have always assumed.
Although human adults are made up of trillions of cells, we all start out as a single cell, the fertilized egg. This divides to become 2 cells which in turn divide to become 4 which become 8 and so on. At some point, cells begin to specialize in their function. Like trains sent to different end stations, some will be diverted to become the placenta while others will become the embryo.
Self-destructive embryonic cell
The team of scientists analyzed previously published data on the gene activity of each individual cell of 5-day-old embryos and found that around a quarter of the cells did not fit the profile of any of the known cell types (preembryo, preplacenta, etc.). ).
Investigating further, they discovered that these cells contained so-called “young transposable elements” or “jumping genes.” These are rogue DNA elements that can copy themselves and reinsert themselves into our DNA, often causing damage in the process.
Embryo staining carried out by project collaborators in Spain confirmed the existence of cells with proteins derived from jumping genes.
Looking a bit further in time, the team discovered that their descendants had DNA damage and underwent a process of programmed cell death.
Quality control mechanism
This process, the researchers suggest, looks like a form of quality control: selection among cells in favor of the good ones.
Dr. Zsuzsanna Izsva?k, co-lead author from the Max Delbrück Center and an expert in mobile DNA, said: “Humans, like all organisms, fight an endless game of cat and mouse with these harmful jumping genes.
“While we try to suppress these jumping genes by any means possible, very early in development they are active in some cells, probably because we can’t activate our genetic defenses fast enough.”
Co-lead author Professor Laurence Hurst, from the Milner Center for Evolution at the University of Bath, said: “If a cell is damaged by jumping genes, or any other type of error, such as having too few or too many chromosomes, – then it is better for the embryo to remove these cells and not allow them to become part of the developing baby.
“We are used to the idea that natural selection favors one organism over another. What we are seeing inside embryos also looks like survival of the fittest, but this time among nearly identical cells. It seems we have discovered a new part of our arsenal — against these damaging genetic components.”
Using old genetic enemies to fight new ones
In contrast, the single-cell data showed that the key cells that will become the embryo (the inner cell mass, or ICM) do not contain jumping genes, but instead express a virus-like gene called endogenous human H virus. This it helps suppress young jumping genes in the inner cell mass, fitting with an emerging pattern that we use our old genetic enemies to fight new ones.
The authors suggest that if the quality control process is too sensitive, the embryo as a whole may die. This could explain why some mutations in our system for detecting damage in early embryos are also associated with infertility.
https://www.sciencedaily.com/releases/2023/06/230620174450.htm
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