Neural Crest Stem Cell Discovery Casts Doubt on Cellular Reprogramming Assumptions

A University of Toronto research team has challenged prevailing theories in cellular reprogramming, proposing that neural crest stem cells (NCSCs) are the true source of reprogrammed neurons. This discovery contradicts the widely accepted notion that any mature cell can be induced to change its identity through the infusion of transcription factors.

The study, published in Stem Cell Reports, suggests that NCSCs, found in skin and other tissues, are uniquely capable of being reprogrammed into various cell types. Justin Belair-Hickey, the study's first author, explains, "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."

NCSCs, located beneath hair follicles in the skin, are genetically predisposed to develop into neurons. This aligns with their embryonic origin in the ectodermal germ layer, which also gives rise to many skin cell types.

The research team hypothesized that cellular reprogramming is limited to stem cells and mature cells from the same germ layer. They argue that previous interpretations of experimental data may have overstated the flexibility of cell identity.

“I think claims about direct reprogramming are either overstated or based on inaccurate interpretations of the data,” said Belair-Hickey. “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’ve found skin cells that can be reprogrammed into neurons, but what we’ve actually found are stem cells in the skin that are derived from the brain.”

“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,” said Derek van der Kooy, principal investigator on the study. “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’ve found is a unique group of stem cells that can be studied to understand the true potential of cell reprogramming.”