The tiny fingers that touch stem cells

Author: David Kent, 09/22/15

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I was reading Nature the other day and came across a neat article from Yukikio Yamashita’s group at the University of Michigan entitled Nanotubes mediate niche–stem-cell signalling in the Drosophila testis. It may not sound interesting to our average reader, but the cool thing – and presumably what the Nature editors and reviewers enjoyed – is that it is the first study to really dissect the mechanism of how stem cells specifically communicate with their niche.

The stem cell niche is the all-encompassing term that researchers apply to the physical cellular environment that a stem cell lives in. It provides the necessary external signals to retain stem cell identity, and cells that find themselves outside of this environment rapidly lose their ability to make more stem cells. If researchers could figure out how to create this niche artificially, then they could direct the fate of stem cells to make more stem cells in order to have an unlimited pool from which to create cells for transplantation, blood transfusions, and multiple regenerative medicine procedures – a cellular gold mine.

The Yamashita paper on nanotubes was particularly interesting because it identified small projections that emerged from the supportive niche cells to interact with, and supply, the necessary signals to stem cells in a highly specific way (e.g., the nanotubes are really thin and tiny and are only in contact with the stem cell populations, not the other cell types). The nanotubes deliver specific molecules to the stem cells that permit them to undergo self-renewal divisions (in other words, to make another stem cell when it divides) and the paper goes on to show that if you remove a specific molecule supplied by nanotubes, or the nanotubes themselves, the whole system falls apart (i.e., a stem cell’s ability to make more stem cells is dramatically reduced).

Funnily enough, it reminded me of something we observed, but never published, from a study I was involved with years ago with Eric Jervis’ group at the University of Waterloo (now at STEMCELL Technologies). The Jervis group was making time-lapse movies of blood stem cells that we’d sent to them in order to see how a stem cell’s very first progeny behaved in terms of their growth rates and maturation, and occasionally we would see these really interesting connections between cells. It seemed that immediately after division, the progeny of some portion of the blood stem cells we were observing did not want to leave their siblings and retained or re-created tiny cellular bridges between them (see inset). Perhaps this was an effort to search for the missing signals needed to undergo self-renewal. Maybe it’s time to resurrect that line of thinking?

Mouse blood stem cells can keep in touch with each other many hours after dividing using cellular bridges.

Mouse blood stem cells can keep in touch with each other many hours after dividing using cellular bridges.

Two major implications arise from the Yamashita nanotube paper. The first is for designers of artificial niches: perhaps micro-patterned surfaces are required to help direct stem cell fate decisions? The second is that nanotubes, if identified in other stem cell niches, could be studied to identify the exact factors required to support stem cell expansion and allow researchers to target those molecules selectively.

In the end, the science is really exciting: tiny little projections from cells hold the key to stem cell expansion and the potential is there to exploit this knowledge for regenerative medicine applications. Despite being discovered in fruit flies, nanotubes could be a real game changer for researchers who think about the supportive environment that allows a stem cell to make equally potent copies of itself.

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David Kent

David Kent

Principal Investigator at University of Cambridge
Dr. David Kent is a Principal Investigator at the University of Cambridge in the Cambridge Stem Cell Institute (http://www.stemcells.cam.ac.uk/researchers/principal-investigators/dr-david-kent). His laboratory's research focuses on fate choice in single blood stem cells and how changes in their regulation lead to cancers. David is currently the Stem Cell Institute’s Public Engagement Champion and has a long history of public engagement and outreach including the creation of The Black Hole in 2009. He has been writing for Signals since 2010.
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