A new study reveals that human embryonic cells can enter a dormant state similar to diapause, a survival strategy used by some mammals to temporarily halt development.
Summary: Researchers have found that human stem cells and embryo models can be induced to enter a reversible dormant state by inhibiting a key molecular pathway, mimicking embryonic diapause seen in other mammals.
Estimated reading time: 5 minutes
Scientists have uncovered a molecular “pause button” for early human development, potentially opening new avenues for reproductive medicine and embryo research. The groundbreaking study, published in the journal Cell on September 26, 2024, demonstrates that human cells can enter a diapause-like state of suspended animation, previously observed only in certain mammal species.
A team of researchers from the Max Planck Institute for Molecular Genetics in Berlin and the Institute of Molecular Biotechnology (IMBA) in Vienna used stem cell-derived models to investigate whether human cells could respond to diapause triggers. Their findings suggest that humans may retain the ability to temporarily slow down embryonic development, even though this mechanism is not naturally utilized during pregnancy.
Mimicking Diapause in Human Cells
Embryonic diapause is a reproductive strategy employed by some mammals to delay implantation and extend pregnancy. This phenomenon typically occurs at the blastocyst stage, just before the embryo attaches to the uterus. During diapause, the embryo remains in a state of suspended animation for weeks or months until conditions are favorable for continued development.
To study this process in human cells without using actual embryos, the researchers turned to stem cells and blastoids – laboratory-grown structures that mimic early embryos. By modulating a specific molecular pathway called mTOR signaling, they were able to induce a dormant state remarkably similar to diapause.
“The mTOR pathway is a major regulator of growth and developmental progression in mouse embryos,” says Aydan Bulut-Karslioglu, one of the study’s lead authors. “When we treated human stem cells and blastoids with an mTOR inhibitor we observed a developmental delay, which means that human cells can deploy the molecular machinery to elicit a diapause-like response.”
The induced dormant state exhibited several key characteristics:
- Reduced cell division
- Slower overall development
- Decreased ability to attach to uterine lining cells
Importantly, the researchers found that this dormancy was reversible. When the mTOR inhibition was removed, the cells resumed normal development.
A Time-Limited Window for Dormancy
One intriguing aspect of the study is that the ability to enter this dormant state appears to be restricted to a specific developmental period. Dhanur P. Iyer, a shared first author of the study, explains: “The developmental timing of blastoids can be stretched around the blastocyst stage, which is exactly the stage where diapause works in most mammals.”
This finding aligns with observations in other species where diapause naturally occurs, suggesting a conserved evolutionary mechanism.
Implications for Reproductive Medicine
The discovery of this latent ability in human cells could have significant implications for reproductive medicine, particularly in the field of in vitro fertilization (IVF). Nicolas Rivron, another lead researcher on the project, outlines two potential applications:
- Enhancing mTOR activity could potentially speed up embryo development, which is known to increase IVF success rates.
- Inducing a dormant state during IVF procedures could provide a larger time window to assess embryo health and improve synchronization with the mother for better implantation.
“Although we have lost the ability to naturally enter dormancy, these experiments suggest that we have nevertheless retained this inner ability and could eventually unleash it,” Rivron states.
Ethical Considerations and Future Research
It’s important to note that this research was conducted using stem cell models and not actual human embryos, sidestepping potential ethical concerns. The use of blastoids provides a scientific and ethical alternative for studying early human development.
The study raises intriguing questions about the evolutionary history of human development and opens new avenues for research. Future studies may investigate whether human and other mammalian cells enter dormant states through similar or alternative pathways, and explore the purposes of this ability across species.
Heidar Heidari Khoei, a postdoctoral fellow and co-first author of the study, emphasizes the collaborative nature of the research: “This exciting collaboration is a testimony to how complex biological questions can be tackled by bringing together respective expertise. I believe this work not only underscores the importance of collaboration in advancing science but also opens up further possibilities for understanding how various signals are perceived by cells as they prepare for their developmental journey.”
As scientists continue to unravel the mysteries of early human development, this newfound ability to induce and reverse cellular dormancy may prove to be a powerful tool in both basic research and clinical applications.
Quiz
- What molecular pathway did researchers manipulate to induce a dormant state in human cells?
- At which stage of embryonic development does diapause typically occur in mammals?
- Name two potential implications of this research for in vitro fertilization (IVF).
Answers:
- The mTOR signaling pathway
- The blastocyst stage
- a) Enhancing mTOR activity could speed up embryo development and increase IVF success rates. b) Inducing dormancy could provide more time to assess embryo health and improve synchronization with the mother for better implantation.
For further reading:
- Original research article in Cell: mTOR activity paces human blastocyst stage developmental progression
Glossary of Terms
- Diapause: A temporary pause in embryonic development used by some mammals to delay implantation and extend pregnancy.
- Blastocyst: An early stage of embryonic development, typically consisting of 50-100 cells, that occurs before implantation in the uterus.
- mTOR signaling: A molecular pathway that regulates cell growth, proliferation, and survival in response to nutrients and growth factors.
- Blastoids: Laboratory-grown structures that mimic early embryos, used as an ethical alternative to studying actual human embryos.
- In vitro fertilization (IVF): A medical procedure in which an egg is fertilized by sperm outside the body and then implanted in the uterus.
- Stem cells: Undifferentiated cells that can develop into various specialized cell types and self-renew to produce more stem cells.
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