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Wnt pathway appears key to cell reprogramming

Colony of iPSCs

Salk Institute

The Wnt signaling pathway plays a key role in the generation of induced pluripotent stem cells (iPSCs), according to a study published in Stem Cell Reports.

Researchers found they could increase the efficiency of the cell reprogramming process by inhibiting the Wnt pathway.

“[U]ntil now, this was a very inefficient process,” said study author Ilda Theka, a PhD student at the Centre for Genomic Regulation in Barcelona, Spain.

“There are many groups trying to understand the mechanism by which adult cells become pluripotent and what blocks that process and makes only a small percentage of cells end up being reprogrammed. We are providing information on why it happens.”

The researchers studied how the Wnt pathway behaves throughout the process of transforming mature cells into iPSCs, which usually lasts 2 weeks. It’s a dynamic process that produces oscillations from the pathway, which is not active all the time.

“We have seen that there are two phases and that, in each one of them, Wnt fulfils a different function,” Theka said. “And we have shown that, by inhibiting it at the beginning of the process and activating it at the end, we can increase the efficiency of reprogramming and obtain a larger number of pluripotent cells.”

The team also discovered that the exact moment when the Wnt pathway is activated is crucial. Activating the pathway too early makes the cells begin to differentiate, and they are not reprogrammed.

To artificially control the pathway, the researchers used a molecule called Iwp2, a Wnt-secretion inhibitor that does not permanently alter the cells.

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Colony of iPSCs

Salk Institute

The Wnt signaling pathway plays a key role in the generation of induced pluripotent stem cells (iPSCs), according to a study published in Stem Cell Reports.

Researchers found they could increase the efficiency of the cell reprogramming process by inhibiting the Wnt pathway.

“[U]ntil now, this was a very inefficient process,” said study author Ilda Theka, a PhD student at the Centre for Genomic Regulation in Barcelona, Spain.

“There are many groups trying to understand the mechanism by which adult cells become pluripotent and what blocks that process and makes only a small percentage of cells end up being reprogrammed. We are providing information on why it happens.”

The researchers studied how the Wnt pathway behaves throughout the process of transforming mature cells into iPSCs, which usually lasts 2 weeks. It’s a dynamic process that produces oscillations from the pathway, which is not active all the time.

“We have seen that there are two phases and that, in each one of them, Wnt fulfils a different function,” Theka said. “And we have shown that, by inhibiting it at the beginning of the process and activating it at the end, we can increase the efficiency of reprogramming and obtain a larger number of pluripotent cells.”

The team also discovered that the exact moment when the Wnt pathway is activated is crucial. Activating the pathway too early makes the cells begin to differentiate, and they are not reprogrammed.

To artificially control the pathway, the researchers used a molecule called Iwp2, a Wnt-secretion inhibitor that does not permanently alter the cells.

Colony of iPSCs

Salk Institute

The Wnt signaling pathway plays a key role in the generation of induced pluripotent stem cells (iPSCs), according to a study published in Stem Cell Reports.

Researchers found they could increase the efficiency of the cell reprogramming process by inhibiting the Wnt pathway.

“[U]ntil now, this was a very inefficient process,” said study author Ilda Theka, a PhD student at the Centre for Genomic Regulation in Barcelona, Spain.

“There are many groups trying to understand the mechanism by which adult cells become pluripotent and what blocks that process and makes only a small percentage of cells end up being reprogrammed. We are providing information on why it happens.”

The researchers studied how the Wnt pathway behaves throughout the process of transforming mature cells into iPSCs, which usually lasts 2 weeks. It’s a dynamic process that produces oscillations from the pathway, which is not active all the time.

“We have seen that there are two phases and that, in each one of them, Wnt fulfils a different function,” Theka said. “And we have shown that, by inhibiting it at the beginning of the process and activating it at the end, we can increase the efficiency of reprogramming and obtain a larger number of pluripotent cells.”

The team also discovered that the exact moment when the Wnt pathway is activated is crucial. Activating the pathway too early makes the cells begin to differentiate, and they are not reprogrammed.

To artificially control the pathway, the researchers used a molecule called Iwp2, a Wnt-secretion inhibitor that does not permanently alter the cells.

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