News | New Scientific Finding: How Transposons Affect Early Human Development
A new study found that a major transition in early human development is governed not by our own genes, but by DNA elements called transposons. Conducted by researchers at Sinai Health, the study challenges conventional views of these mysterious DNA fragments and reveals their important roles in human development and disease.
"People tend to think of transposons as virus-like parasites that hijack our cells to reproduce themselves," said Dr. Miguel Ramalho-Santos, senior co-author and senior investigator at the Lunenfeld-Tanenbaum Research Institute. "But our study found that these elements are not merely genomic parasites; they are essential to early development."
Published in Developmental Cell, the study shows that transposable elements play a key role in ensuring human embryonic cells progress normally through early development rather than reverting to an earlier state. The researchers focused on LINE-1, or long interspersed nuclear element-1. Rather than merely accompanying the genes that make up less than 2% of our genome, LINE-1 elements account for 20% of the genetic material in cells. Some can amplify themselves, move through the genome, and insert into new locations, earning the label "selfish DNA."
Scientists have long considered these elements largely harmful because they can disrupt the genome and cause diseases including hemophilia, neurological disorders, and cancer.
Dr. Juan Zhang, a postdoctoral fellow and another senior co-author, first became interested in the abundant LINE-1 RNA messages in early embryos. RNA messages are transcribed from active portions of the genome, indicating that LINE-1 elements are active during these critical early stages.
"If transposons are harmful, why are they active in the early embryo? This is an embryo just beginning to form. Any dangerous insertion would propagate throughout the individual's development," Dr. Zhang said.
When LINE-1 expression was suppressed in cultured human embryonic stem cells (ESCs), the cells regressed to a more primitive eight-cell stage. At that stage, the eight identical totipotent cells can develop into both the embryo and placenta. Beyond this stage, ESCs can still form all fetal cell types but gradually lose the ability to contribute to the placenta.
Further experiments showed that these LINE-1 RNA molecules act as scaffolds that organize DNA within the three-dimensional space of the cell nucleus. They help move chromosome 19, which contains key genes, into a gene-silencing region, allowing the embryo to progress smoothly to later stages.
"Our study shows that LINE-1 regulates gene expression at the critical transition when the embryo begins specializing its cells for different functions. Our results suggest this is not accidental, but an important evolutionary mechanism," Dr. Zhang said.
Surprisingly, this new role runs counter to LINE-1's usual behavior. Rather than jumping to new genomic locations and causing potentially harmful mutations, LINE-1 elements specifically promote development in this critical context, underscoring their importance in early human growth.
This basic research has important implications for fertility treatment and the use of stem cells in regenerative medicine. It also reveals a new role for LINE-1 that can be explored in diseases involving these elements, including neurological disorders and cancer.
Dr. Anne-Claude Gingras, director of the Lunenfeld-Tanenbaum Research Institute and vice president of research, said, "This study highlights how much more we have to learn about human development and these mysterious genomic elements. I congratulate my colleagues for breaking new ground with this important discovery and look forward to what their continuing research will reveal."
The study was funded by the Canadian Institutes of Health Research, the Great Gulf Homes Charitable Foundation, and the University of Toronto Medicine by Design program.
News | New Scientific Finding: How Transposons Affect Early Human Development
News | New Scientific Finding: How Transposons Affect Early Human Development
A new study found that a major transition in early human development is governed not by our own genes, but by DNA elements called transposons. Conducted by researchers at Sinai Health, the study challenges conventional views of these mysterious DNA fragments and reveals their important roles in human development and disease.
"People tend to think of transposons as virus-like parasites that hijack our cells to reproduce themselves," said Dr. Miguel Ramalho-Santos, senior co-author and senior investigator at the Lunenfeld-Tanenbaum Research Institute. "But our study found that these elements are not merely genomic parasites; they are essential to early development."
Published in Developmental Cell, the study shows that transposable elements play a key role in ensuring human embryonic cells progress normally through early development rather than reverting to an earlier state. The researchers focused on LINE-1, or long interspersed nuclear element-1. Rather than merely accompanying the genes that make up less than 2% of our genome, LINE-1 elements account for 20% of the genetic material in cells. Some can amplify themselves, move through the genome, and insert into new locations, earning the label "selfish DNA."
Scientists have long considered these elements largely harmful because they can disrupt the genome and cause diseases including hemophilia, neurological disorders, and cancer.
Dr. Juan Zhang, a postdoctoral fellow and another senior co-author, first became interested in the abundant LINE-1 RNA messages in early embryos. RNA messages are transcribed from active portions of the genome, indicating that LINE-1 elements are active during these critical early stages.
"If transposons are harmful, why are they active in the early embryo? This is an embryo just beginning to form. Any dangerous insertion would propagate throughout the individual's development," Dr. Zhang said.
When LINE-1 expression was suppressed in cultured human embryonic stem cells (ESCs), the cells regressed to a more primitive eight-cell stage. At that stage, the eight identical totipotent cells can develop into both the embryo and placenta. Beyond this stage, ESCs can still form all fetal cell types but gradually lose the ability to contribute to the placenta.
Further experiments showed that these LINE-1 RNA molecules act as scaffolds that organize DNA within the three-dimensional space of the cell nucleus. They help move chromosome 19, which contains key genes, into a gene-silencing region, allowing the embryo to progress smoothly to later stages.
"Our study shows that LINE-1 regulates gene expression at the critical transition when the embryo begins specializing its cells for different functions. Our results suggest this is not accidental, but an important evolutionary mechanism," Dr. Zhang said.
Surprisingly, this new role runs counter to LINE-1's usual behavior. Rather than jumping to new genomic locations and causing potentially harmful mutations, LINE-1 elements specifically promote development in this critical context, underscoring their importance in early human growth.
This basic research has important implications for fertility treatment and the use of stem cells in regenerative medicine. It also reveals a new role for LINE-1 that can be explored in diseases involving these elements, including neurological disorders and cancer.
Dr. Anne-Claude Gingras, director of the Lunenfeld-Tanenbaum Research Institute and vice president of research, said, "This study highlights how much more we have to learn about human development and these mysterious genomic elements. I congratulate my colleagues for breaking new ground with this important discovery and look forward to what their continuing research will reveal."
The study was funded by the Canadian Institutes of Health Research, the Great Gulf Homes Charitable Foundation, and the University of Toronto Medicine by Design program.
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