A team led by researchers at the University of Toronto has discovered that a group of cells located in the skin and other areas of the body, called neural crest stem cells, are the source of reprogrammed neurons found by other researchers.
Their findings refute the popular theory about cellular reprogramming that any developed cell can be induced to change its identity to a completely unrelated cell type through the infusion of transcription factors. The team proposes an alternative theory: there exists a rare type of stem cell that is unique in its ability to reprogram itself into different cell types.
“We believed that most cases of cellular reprogramming could be attributed to a rare, multipotential stem cell that is found throughout the body and remains dormant within mature cell populations,” said Justin Belair-Hickey, first author of the study and a graduate . student at U of T’s Donnelly Center for Cellular and Biomolecular Research. “It was not fully understood why reprogramming tends to be an inefficient process. Our data explain this inefficiency by showing that the neural crest stem cell is one of the few stem cells that can produce the desired type of reprogrammed cell.
The study was recently published in the journal Stem cell reports.
Neural crest cells, found beneath the hair follicle in the skin, are genetically predisposed to become neurons. This is not unexpected, since many types of skin cells originate in the same place in the embryo as neurons: the ectodermal germ layer. The ectoderm is the outermost of the three cell layers that form during embryonic development.
The team was prompted to conduct this study through their own questioning of how experimental data from cell reprogramming research is interpreted in terms of how flexible a cell’s identity is. This includes theories about how mature cells from one embryonic layer can be directly reprogrammed into mature cells from another embryonic layer, even though the three germ layers are separated by different developmental histories. They hypothesized that cellular reprogramming can only occur from a stem cell to a mature cell, where both come from the same germ layer.
“I think claims about direct reprogramming are exaggerated or based on inaccurate interpretations of the data,” Belair-Hickey said. “We set out to demonstrate that the identity of a cell is much more defined and stable than what the field of cellular reprogramming has proposed. At first glance, it seems that we have found skin cells that can be reprogrammed into neurons, but what we know “In fact, what I have found are stem cells in the skin that are derived from the brain.”
Neural crest stem cells are found throughout the body, including in the skin, bones, and connective tissue. Their distribution throughout the body, their ability to be reprogrammed into many cell types, and their accessibility within the skin for harvesting make them high potential candidates for stem cell transplantation to treat diseases.
“Neural crest stem cells may have gone unnoticed by others studying cellular reprogramming because, while they are widespread throughout the body, they are also rare,” said Derek van der Kooy, the study’s principal investigator and professor of genetics. molecular at the Donnelly Center. and the U of T Temerty School of Medicine. “As such, they may have been confused with mature cells from various tissue types that could be reprogrammed into other cell types. I think what we have found is a unique group of stem cells that can be studied to understand the true potential of cellular reprogramming.”
This research was supported by the Canadian Institutes of Health Research, the Krembil Foundation and Medicine by Design.