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Researchers boost stem cell programming with gene mutation

October 25, 2016 By Sarah Faulkner

Researchers boost stem cell programming with gene mutationResearchers discovered a way to increase the efficiency of stem cell programming using research on a rare genetic disease, according to a study published in the Proceedings of the National Academy of Sciences. 

Induced pluripotent stem cells are created from skin cells and can be transformed into any type of cell in the body. Using existing techniques, according to the team of researchers, fewer than 1% of adult skin cells are reprogrammed into induced pluripotent stem cells.

“Inefficiency in creating iPSCs is a major roadblock toward applying this technology to biomedicine,” Dr. Shinya Yamanaka, the Nobel-prize-winning researcher who discovered iPSCs, said in prepared remarks. “Our study identified a surprising way to increase the number of iPSCs that we can generate.”

The researchers were trying to create a model to study fibrodyslasia ossificans progressiva, a rare genetic disease that causes muscles, tendons and ligaments to turn into bone. A mutation in the ACVR1 gene over-stimulates a cellular signaling process that’s important for embryonic development and involves a protein known as BMP.

The team discovered they could create more of the induced pluripotent stem cells from patients with the rare disease. They hypothesized that this boost to stem cell programming may be because BMP signaling improves cell renewal and keeps the cells in a pluripotent state. When the team prevented BMP signaling, fewer iPSCs were generated from the patients’ cells and the opposite was also true; activating the BMP signaling pathway yielded more of the iPSCs.

“Originally, we wanted to establish a disease model for FOP that might help us understand how specific gene mutations affect bone formation,” lead author Yohei Hayashi explained. “We were surprised to learn that cells from patients with FOP reprogrammed much more efficiently than cells from healthy patients. We think this may be because the same pathway that causes bone cells to proliferate also helps stem cells to regenerate.”

“This is is the first reported case showing that a naturally occurring genetic mutation improves the efficiency of iPSC generation,” co-author Dr. Bruce Conklin said. “Creating iPSCs from patient cells carrying genetic mutations is not only useful for disease modeling, but can also offer new insights into the reprogramming process.”

Filed Under: Featured, Research & Development, Stem Cells

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