Priming stem cells to specialise

What is it about?

Stem cells give rise to specialised cells in a process called differentiation. This is critical for adult tissues to replenish cells lost due to natural turnover or regenerate after injury. We know that stem cells reside in a specialised environment called a niche, which allows them to remain as stem cells. Loss of signals from the niche leads to loss of stem cells, leading people to assume that differentiation was a default state when stem cells could not self-renew. We show here that this is not the case, and that differentiation is an active process that occurs in multiple stages and not simply as a consequence of losing niche signals.

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Photo by FLY:D on Unsplash

Photo by FLY:D on Unsplash

Why is it important?

This work challenges our view of how stem cells self-renew and differentiate. We show that, although the niche is critical to maintain self-renewal, there are also differentiation signals. Removing both niche and differentiation signals allows stem cells to continue self-renewing. Secondly, we show that differentiation is not an irreversible path once cells embark on it. Instead, there are several steps, where we identify first a stage where cells are "primed" or "licensed", meaning that they are able to differentiate but not committed to this fate. Commitment only happens once licensed cells receive a second signal coming from neighbouring cells, so that they all differentiate together. In summary, this work shows that the niche is only one of the environments regulating stem cell fate, but that differentiation is also regulated and occurs in stages, with the first one, called priming or licensing, being a reversible state. This means that understanding how stem cells build and maintain tissues requires more than just understanding signals from the niche, but instead we need to consider how differentiation is induced.