Researchers from UCSD have found in a recent study using Goltz syndrome that Wnt proteins, regulators of cell interaction during embryogenesis, are crucial to the process of cellular reprogramming. Their study, led by principal investigator and assistant professor in the Department of Cellular and Molecular Medicine Dr. Karl Willert, was published in the Nov. 20 online issue of Cell Reports.
For the past six years, Willert’s lab has focused on the unique role of Wnt proteins in the regulation of stem cell behavior. These proteins are also present in areas of the body where there exist high stem cell populations throughout adult life.
His most recently published study used a rare human syndrome called focal dermal hypoplasia, or Goltz syndrome, to determine what effect Wnt proteins have on the reprogramming of skin cells back into embryonic-like stem cells called induced pluripotent stem cells, or iPS cells.
Goltz syndrome is a genetic disorder that primarily produces abnormalities of the skin, skeleton, eyes and face. It is an extremely rare disease, with only 200 to 300 cases documented worldwide, which makes it difficult to collect samples to perform experiments with. In order to collect the necessary biopsies to conduct his studies, Willert traveled to Orlando, Florida, where he attended a meeting with families who are affected by Goltz syndrome. Once there, he collected skin biopsies from 10 different patients with varying degrees of the condition to use for the study.
Researchers at UCSD then used the PORCN gene, a gene that is essential to activating Wnt proteins but is mutated in those affected by Goltz syndrome, from the samples to abolish any Wnt signaling within the skin cells.
As a result, it became impossible to reprogram the skin cells back into iPS cells. Willert and his team determined from these findings that Wnt signaling was needed to establish the linking route necessary in reprogramming cells.
“We found it to be absolutely required,” Willert told the UCSD Guardian. “It cannot be done without these signals.”
The goal of the studies conducted within his lab is to understand how Wnt proteins affect different biological processes, but recent findings could also be important to future medicine, according to Willert.
As Wnt signaling has been found to be important in cell regrowth, one idea is to block these signals with genes such as PORCN in order to treat cancer. However, this idea is precarious, Willert said, as Wnt is so essential to many other functions within the body, such as the maintenance of the intestinal tracts.
Wnt proteins are also being considered as a future regenerative medicine, an idea inspired by certain animals’ ability to regenerate limbs through the reawakening of pathways present in stages of embryogenesis. Since Wnt signaling is present and crucial during this period, it is believed that this signaling could also be used to promote tissue regeneration and growth in wound healing.
“For right now, I’ll settle for regrowth of skin that’s been damaged because of a cut,” Willert said. “But in the future, these Wnt proteins have great potential for regenerative medicine.”
