Scientists at Michigan State University say they have found that a gene known as ASF1A could be critical to the development of stem cells. ASF1A is at least one of the genes responsible for the mechanism of cellular reprogramming, a phenomenon that can turn one cell type into another, which is key to the making of stem cells, according to the researchers.
In a paper (“Histone chaperone ASF1A is required for maintenance of pluripotency and cellular reprogramming”) published in Science, the MSU team describes how they analyzed more than 5,000 genes from a human oocyte before determining that the ASF1A, along with another gene known as OCT4 and a helper soluble molecule, were the ones responsible for the reprogramming.
“This has the potential to be a major breakthrough in the way we look at how stem cells are developed,” said Elena Gonzalez-Munoz, Ph.D., a former MSU post-doctoral researcher and first author of the paper. “Researchers are just now figuring out how adult somatic cells such as skin cells can be turned into embryonic stem cells. Hopefully this will be the way to understand more about how that mechanism works.”
In 2006, an MSU team identified the thousands of genes that reside in the oocyte. It was from those, they concluded, that they could identify the genes responsible for cellular reprogramming. In 2007, a team of Japanese researchers found that by introducing four other genes into cells, induced pluripotent stem cells (iPSCs) could be created without the use of a human egg. “This is important because the iPSCs are derived directly from adult tissue and can be a perfect genetic match for a patient,” said Jose Cibelli, Ph.D., an MSU professor of animal science and a member of the team.
The researchers say that the genes ASF1A and OCT4 work in tandem with a ligand, a hormone-like substance that also is produced in the oocyte called GDF9, to facilitate the reprogramming process.
“We also show that overexpression of just ASF1A and OCT4 in hADFs exposed to the oocyte-specific paracrine growth factor GDF9 can reprogram hADFs into pluripotent cells,” wrote the investigators. “Our report underscores the importance of studying the unfertilized MII [metaphase II human] as a means to understand the molecular pathways governing somatic cell reprogramming.”
“We believe that ASF1A and GDF9 are two players among many others that remain to be discovered, which are part of the cellular-reprogramming process,” noted Dr. Cibelli. “We hope that in the near future, with what we have learned here, we will be able to test new hypotheses that will reveal more secrets the oocyte is hiding from us. In turn, we will be able to develop new and safer cell therapy strategies.”