Scientists generally agree that cells are self-contained units, with the human genome — made up of chromosomes, which are comprised of our genes and DNA — residing in the cell's nucleus.  

When cells divide through mitosis, they pass on the genetic information carried in their chromosomes down to their daughter cells, including any genetic mutations caused by radiation or infections. But what if segments of DNA could also move between cells through an entirely different process?

A new study published in the journal Cell reveals just that: an alternate, previously unknown, route for DNA to travel between cells. Scientists from the Children's Medical Center Research Institute at UT Southwestern and the Oklahoma Medical Research Foundation found that in some cases when chromosomes failed to divide equally, DNA fragments remained behind in tiny sacs called micronuclei, which float in the cell's cytoplasm rather than the nucleus. Using fluorescently tagged Allen Institute cell lines, the researchers observed these micronuclei migrating from one cell to another carrying their DNA passengers with them, which was a surprising discovery.

“This has been well-established in organisms such as bacteria through a process called horizontal gene transfer, where bacteria share DNA with neighboring bacteria, allowing them to acquire a new function, such as resistance to antibiotics,” said Peter Ly, Assistant Professor in the Children’s Medical Center Research Institute at UT Southwestern and senior author of the study. “But we were not aware of this type of transfer before in human cells.”

Time-lapse movie of live hiPS cell colony expressing mTagRFP-T-tagged lamin B1. A single, mid-level plane of the cells was imaged every 3 min on a spinning-disk confocal microscope. Movie plays at 1800x real time. Scale bar, 5 µm.

Ly’s team found that in cases of genomic instability, donor cells transferred micronuclei to recipient cells through bridge-like structures called nanotubes. The transfer occurred across multiple human cell types, including retinal pigment epithelial cells, kidney cells, and cancer cells. Ly then collaborated with OMRF scientists who work with human induced pluripotent stem cells (iPSCs) to confirm the phenomenon in stem cells.

“We were looking at this in a two-dimensional culture, but in actual human tissue where cells are packed together very tightly, you might anticipate that this would occur even more frequently,” said Gary Gorbsky, OMRF professor and study co-author. “This opens up the possibility of a new process of genetic transfer of information.”

What effect did rogue DNA have on the new cell?

To test whether this new DNA that came from another cell had a functional impact on the new cell, the scientists engineered donor cells with resistance to a specific antibiotic. After combining donor and recipient cells in culture and inducing chromosome damage, they found that recipient cells acquired the same antibiotic resistance – direct evidence that mammalian cells can trade genetic material through simple cell-to-cell contact.

“One exciting aspect of the study was that once the DNA transfers, it can actually become a part of that recipient cell’s genome, express genes, and change the function of that cell,” Ly said.

Scientists are still researching the full implications of these findings and the extent that recipient cells could be infected by damaged DNA, but they’re actively exploring those areas.  

The work relied on Allen Institute cell lines AICS-0012 and AICS-0034, which express fluorescently-tagged proteins specific to the research: alpha-tubulin in the case of AICS-0012, and lamin B1 in the case of AICS-0034.

“All of the iPSC lines offered by Allen Institute are derived from the same parental cell line, providing a shared genetic background, which is crucial to our study of genomic instability,” said Maria Narozna, OMRF researcher and study co-author. “The diverse number of genes that are endogenously tagged and made available from the Institute allows you to design experiments creatively and gives you the specific answer you’re looking for.”

Looking ahead, the researchers hope to determine how this form of DNA transfer might contribute to how cancer spreads. For now, they're excited about its broader implications for how genetic instability may propagate through tissues.

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