The Role of Neural Crest Stem Cells in Cellular Reprogramming

Researchers at the University of Toronto have identified that neural crest stem cells, a group of cells located in the skin and other parts of the body, are the origin of reprogrammed neurons previously discovered by other scientists.

Their results contradict the widely held belief in cellular reprogramming that transcription factors may be injected into any established cell to cause it to change its identity to a whole other cell type. According to the team's alternate explanation, there is a rare sort of stem cell that is special in that it can be reprogrammed into many cell types.

We believed that most cases of cell reprogramming could be attributed to a rare, multi-potential stem cell that is found throughout the body and lays dormant within populations of mature cells. It was not fully understood why reprogramming tends to be an inefficient process. Our data explain this inefficiency by demonstrating that the neural crest stem cell is one of the few stem cells that can produce the desired reprogrammed cell type.”

Justin Belair-Hickey, Study First Author and Graduate Student, University of Toronto

The study was published in the journal Stem Cell Reports.

The skin's neural crest cells, located beneath hair follicles, have a hereditary predisposition to become neurons. Given that many skin cell types come from the same place in the embryo as neurons in the ectodermal germ layer, this is not surprising. The outermost of the three cell layers that grow during embryonic development is called the ectoderm.

The team's doubts about the interpretation of experimental results from cellular reprogramming studies on the degree of flexibility of a cell's identity motivated them to carry out this investigation.

Even though the three germ layers have distinct developmental histories, some ideas suggest mature cells from one embryonic layer can be directly converted to mature cells from another embryonic layer. They postulate that cellular reprogramming can only take place when a stem cell and a mature cell originate from the same germ layer.

I think claims about direct reprogramming are either overstated or based on inaccurate interpretations of the data. We set out to demonstrate that the identity of a cell is much more defined and stable than the field of cellular reprogramming has proposed. At first glance, it appears that we have found skin cells that can be reprogrammed into neurons, but what we have found are stem cells in the skin that are derived from the brain.”

Justin Belair-Hickey, Study First Author and Graduate Student, University of Toronto

Skin, bone, and connective tissue are among the body's many locations for neural crest stem cells. They are a high-potential option for stem cell transplantation to treat disease because of their distribution throughout the body, capacity to be reprogrammed into a variety of cell types, and accessibility for collection within the skin.

Neural crest stem cells may have gone unnoticed by others studying cell reprogramming because, while they are widespread throughout the body, they are also rare. As such, they may have been mistaken for mature cells of various types of tissue 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 cell reprogramming.”

Derek van der Kooy, Study Principal Investigator and Professor, University of Toronto