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Maintaining stem cell pluripotency

Induced pluripotent stem cells

Salk Institute

Retrotransposons—viral elements incorporated into the human genome—may play a key role in maintaining stem cell pluripotency, a new study suggests.

Previous research indicated that an important fraction of mammalian transcriptomes consists of transcripts derived from retrotransposon elements, but the biological function of these transcripts was unknown.

Now, experiments in induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) have provided some insight into the transcripts’ function.

Piero Carninci, PhD, of RIKEN Center for Life Science Technologies in Yokohama, Japan, and his colleagues described these findings in Nature Genetics.

The researchers found that thousands of transcripts in stem cells that have not yet been annotated are transcribed from retrotransposons, presumably to elicit nuclear functions. These transcripts were expressed in iPSCs and ESCs but not in differentiated cells.

Furthermore, several of the transcripts were shown to be involved in the maintenance of pluripotency. Degrading them using RNA interference caused iPSCs to lose their pluripotency and differentiate.

The researchers said these transcripts appear to have been recruited, both in the human and mouse genome, where they are used to maintain the pluripotency of stem cells. But more research is needed to determine exactly how and why this occurs.

“Our work has just begun to unravel the scale of unexpected functions carried out by retrotransposons and their derived transcripts in stem cell biology,” Dr Carninci said.

“We were extremely surprised to learn from our data that what was once considered genetic junk—namely, ancient retroviruses that were thought to just parasite the genome—are, in reality, symbiotic elements that work closely with other genes to maintain [iPSCs and ESCs] in their undifferentiated state.”

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Induced pluripotent stem cells

Salk Institute

Retrotransposons—viral elements incorporated into the human genome—may play a key role in maintaining stem cell pluripotency, a new study suggests.

Previous research indicated that an important fraction of mammalian transcriptomes consists of transcripts derived from retrotransposon elements, but the biological function of these transcripts was unknown.

Now, experiments in induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) have provided some insight into the transcripts’ function.

Piero Carninci, PhD, of RIKEN Center for Life Science Technologies in Yokohama, Japan, and his colleagues described these findings in Nature Genetics.

The researchers found that thousands of transcripts in stem cells that have not yet been annotated are transcribed from retrotransposons, presumably to elicit nuclear functions. These transcripts were expressed in iPSCs and ESCs but not in differentiated cells.

Furthermore, several of the transcripts were shown to be involved in the maintenance of pluripotency. Degrading them using RNA interference caused iPSCs to lose their pluripotency and differentiate.

The researchers said these transcripts appear to have been recruited, both in the human and mouse genome, where they are used to maintain the pluripotency of stem cells. But more research is needed to determine exactly how and why this occurs.

“Our work has just begun to unravel the scale of unexpected functions carried out by retrotransposons and their derived transcripts in stem cell biology,” Dr Carninci said.

“We were extremely surprised to learn from our data that what was once considered genetic junk—namely, ancient retroviruses that were thought to just parasite the genome—are, in reality, symbiotic elements that work closely with other genes to maintain [iPSCs and ESCs] in their undifferentiated state.”

Induced pluripotent stem cells

Salk Institute

Retrotransposons—viral elements incorporated into the human genome—may play a key role in maintaining stem cell pluripotency, a new study suggests.

Previous research indicated that an important fraction of mammalian transcriptomes consists of transcripts derived from retrotransposon elements, but the biological function of these transcripts was unknown.

Now, experiments in induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) have provided some insight into the transcripts’ function.

Piero Carninci, PhD, of RIKEN Center for Life Science Technologies in Yokohama, Japan, and his colleagues described these findings in Nature Genetics.

The researchers found that thousands of transcripts in stem cells that have not yet been annotated are transcribed from retrotransposons, presumably to elicit nuclear functions. These transcripts were expressed in iPSCs and ESCs but not in differentiated cells.

Furthermore, several of the transcripts were shown to be involved in the maintenance of pluripotency. Degrading them using RNA interference caused iPSCs to lose their pluripotency and differentiate.

The researchers said these transcripts appear to have been recruited, both in the human and mouse genome, where they are used to maintain the pluripotency of stem cells. But more research is needed to determine exactly how and why this occurs.

“Our work has just begun to unravel the scale of unexpected functions carried out by retrotransposons and their derived transcripts in stem cell biology,” Dr Carninci said.

“We were extremely surprised to learn from our data that what was once considered genetic junk—namely, ancient retroviruses that were thought to just parasite the genome—are, in reality, symbiotic elements that work closely with other genes to maintain [iPSCs and ESCs] in their undifferentiated state.”

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