Meeting Report: Polyploidy in Organ Development, Repair, and Disease

Polyploidy is a conserved and frequently occurring phenomenon whose impact on organismal health and disease is poorly understood.  This first symposium focused on Polyploidy was organized by Don Fox (Duke University), Vicki Losick (MDI Biological Laboratory), and Adrienne Roeder (Cornell University), and took place at the MDI Biological Laboratory in Bar Harbor, Maine on October 13-14, 2018.  The meeting successfully appealed to a wide-range of scientists at different stages of their career from across US and abroad.

The sessions covered research using diverse model systems, including the fruit fly, worm, plant, fungi, zebrafish, and mammalian models.  The meeting topics included the role of polyploidy in organ development, tissue repair and regeneration, cell cycle and chromosome segregation fidelity, size control, and infection and disease.   The talks and posters revealed remarkable commonalities across these systems and several themes emerged.   First, although polyploidy comes in many forms, from whole genome duplication throughout the organism to increased DNA content in specialized mononucleate cells, multinucleate cells, or syncytia, it is almost universally associated with an increase in cell or organismal size.  Adding to the complexity, polyploid cells often alter genome copy number either through amplification or underreplication. The advancement of high resolution imaging and single cell sequencing are now providing mechanistic insight into how polyploid cells increase size and alter their genome.

A second theme is that polyploidization often occurs in response to wounding and tends to increase with age but depending on the organ/tissue can be either beneficial or detrimental to regenerative potential.  A third theme is that mechanical signals, likely from the extracellular environment can induce polyploid cell growth, regulating organ development and speed of wound healing.  In addition, many talks revealed that evolutionarily conserved cell cycle regulators are instrumental in producing polyploid cells and regulating their genome integrity. Polyploidy can prevent cell cycle re-entry, which can be advantageous in blocking tumorigenesis or cell death. While these are in some sense “scheduled” polyploidization events that the organism itself induces, “unscheduled” cellular polyploidy events often lead to disease. In the keynote talk, David Pellman (HHMI/Dana Farber) discussed his model that defects in the nuclear envelope of micronuclei explain how an “unscheduled” genome duplication leads to chromothripsis (a chromosome that appears shattered and randomly stitched back together), which sequencing has shown is very common in human cancers. Infections by parasitic nematodes can trigger the formation of polyploid cells in plant roots and ploidy of infectious yeast strains vary in clinical isolates. One of the conclusions the meeting, which was particularly emphasized by Jeff Doyle (Cornell University), was just how many important open questions remain about polyploidy, indicating there is plenty of exciting research to be done on this emerging field. The next Polyploidy symposium is set for 2020 or 2021.

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