Genome instability triggers intercellular DNA transfer between human cells

Area of Science:

• Cell Biology
• Genetics
• Genomics

Background:

• The mammalian genome is protected within the nucleus during interphase.
• Genomic instability can lead to DNA mislocalization into the cytoplasm (micronuclei or fragmented chromosomes).
• The non-cell-autonomous effects of cytoplasmic DNA on neighboring cells are largely unknown.

Purpose of the Study:

• To investigate whether cytoplasmic DNA can be transferred between adjacent cells.
• To determine the mechanism and consequences of intercellular DNA transfer.

Main Methods:

• Utilized various genomic instability inducers (mitotic spindle poisons, ionizing radiation, Cas9).
• Observed intercellular DNA transfer via contact-dependent, cytoskeleton-based nanotube structures.
• Analyzed DNA fragment inheritance and phenotypic changes in recipient cells.

Main Results:

• Cytoplasmic DNA undergoes intercellular transfer through nanotubes connecting human cells.
• This transfer occurs in both cancerous and non-cancerous cells under diverse genomic instability conditions.
• Transferred DNA fragments are inherited as extrachromosomal elements, conferring heritable phenotypic traits.

Conclusions:

• Direct cell-cell contact facilitates a horizontal gene transfer-like mechanism for propagating genomic instability.
• Intercellular DNA transfer via nanotubes can reshape mammalian genomes and alter recipient cell phenotypes.
• This pathway highlights a novel non-cell-autonomous consequence of genomic instability.