Press Release

Department of Human Genetics
Eccles Institute of Human Genetics
University of Utah

RELEASE DATE: 21 Dec. 2000

Contact:
Connie Barth -- (801) 585-6135
cbarth@genetics.utah.edu

SALT LAKE CITY, Utah -- Scientists at the University of Utah took a bold step recently when they decided to challenge conventional wisdom about the ability of fully differentiated mammalian cells to reverse their developmental process and go back to being stem cells. Amphibian cells do this when replacing a lost limb or tail, but mammalian cells have been thought to be incapable of making this change. In normal, healthy mammals, once a muscle cell, always a muscle cell.

Work published by other scientists in the past couple of years hinted at the possibility that mammalian cells could reverse their specialization, so Drs. Mark Keating and Shannon Odelberg decided to try. They successfully took mouse muscle cells and turned them into stem cells, which are cells that can specialize into many different cell types. These stem cells then re-specialized into cells resembling bone, fat, and cartilage cells in vitro, showing that mammalian cells may indeed have the plasticity necessary for regenerative growth. Their study is being published in the December 22 issue of the journal Cell.

Recent research illustrated that a certain gene, called msx1, probably played a role in normal limb development as well as regenerating limbs in several animals. Additionally, Keating and Odelberg were aware that msx1 prevents early muscle cells in mice from specializing. Putting these clues together, they decided to investigate whether msx1 could cause mammalian cells to change their fate.

Keating and Odelberg began by stimulating mouse muscle cells to turn on the msx1 gene and then monitored the presence of certain specialized muscle proteins. As msx1 turned on, levels of these proteins decreased. Some of the muscle cells then broke apart to create stem cells and began to multiply. These stem cells were placed in growth conditions conducive for specialization of other types of cells, such as bone and cartilage. Results showed that the once-specialized muscle cells now had characteristics of bone, fat, and cartilage, a process that doesn’t occur naturally in mammals.

"The dogma that specialized cells in mammals cannot reverse their specialization process is slowly changing," commented Odelberg. He noted that reversing the specialization of a cell is one of the most important processes in regeneration.

Mark Keating, M.D., a professor of Cardiology and Human Genetics and a Howard Hughes Medical Institute Investigator, is currently at The Children’s Hospital in Boston. Shannon Odelberg, Ph.D., is an assistant professor of Cardiology and a researcher with the Eccles Institute of Human Genetics. Angela Kollhoff, another study author, is currently with the Huntsman Cancer Institute and the Howard Hughes Medical Institute.