DNA is precious; without it, our cells¹ would not be able to survive. As such, it’s kept safely within the confines of the nucleus. The outside world — the cytoplasm — is hostile and full of enzymes ready to slice DNA into smithereens at the slightest exposure.

There is, however, one exception, which occurs when cells are under considerable stress. During stress, DNA can break apart, which can wreak havoc on the rest of the genome. To avoid this, the cell often bundles the damaged DNA into a micronucleus.

It then becomes that cell’s problem to deal with… or does it? Elizabeth Maurais and colleagues have recently shown that human cells can send these spheres of fragmented chromatin to neighbouring cells through microscopic tubes.

Papers have been published showing that mammalian cells can transfer mitochondria to surrounding struggling cells as an alternative energy supply. However, the evidence as to whether this occurs with DNA has been scarce. The overall mechanism, the authors showed, involved tube structures reaching between two cells, which is not too dissimilar to how horizontal gene transfer occurs in bacterial populations:

The authors found that for these tunnels to form, cells need to come into direct contact with each other, although they do note that their live imaging method may not have high enough resolution to detect other methods of transfer that don’t involve tunnels, such as small vesicles. This phenomenon was not exclusive to one cell type, either — fully differentiated epithelial cells and stem cells grown in the same dish also exhibited the same behaviour.

One major question was whether fragmented chromatin was stable once it reaches the other side of the tunnel. After all, couldn’t it be treated as a foreign object by the receiving cell and destroyed?

To investigate this, the authors developed a CRISPR-based system which allowed them to deliberately break the Y chromosome upon addition of the drug doxycycline to the cell cultures. Female cells — which don’t have any Y chromosomes — that had taken up the fragmented DNA underwent single cell RNA-sequencing, which takes a snapshot of all the RNA expressed in individual cells. Sure enough, these female cells started expressing Y chromosome genes, showing that this transferred DNA could not only integrate into the nucleus, BUT was functional once it arrived there. Pretty cool stuff.

Although this work has not been conducted in living organisms yet, it could have profound implications across biology. For instance, in cancer cells, we know that the genome is often highly unstable and DNA breaks are common. Perhaps these nanotubes may permit cancer cells to spread their damaged DNA to nearby healthy cells, driving growth or drug resistance.

I’m intrigued as to how we can study this in a more representative system — perhaps something like spatial transcriptomics may be a good approach, where you can visualise the genes expressed in individual cells within a tissue.

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Notes

1. Well, most of them 🙂 Red blood cells and platelets get rid of their DNA eventually, but need it to develop properly. ↩︎

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