Midbodies, once considered the rubbish of cell division, might have a function beyond their role in getting daughter cells to separate. Researchers show in today's Nature Cell Biology that stem cells and cancer cells collect used midbodies, whereas differentiated cells digest the organelle through autophagy.
“The midbody is now emerging as a signaling center or an organizer for things that may have to do with the stemness of cells,” said Andreas Ettinger, a postdoctoral researcher at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany, who was not involved in this study.
During cytokinesis, a single midbody forms as part of a bridge between daughter cells, and its proteins participate in abscission, the final cut that severs the two cells. Discovered more than a century ago, midbodies had been deemed useless after cell division because they were assumed to be cast off into the extracellular space. Recent work has shown that their fate is not so simple, and cells sometimes keep their midbodies following division and digest them by autophagy.
Stephen Doxsey at the University of Massachusetts Medical School and his colleagues saw that midbodies were prevalent in the stem cell compartments of tissues, such as the testes and hair follicles. Differentiated cells, on the other hand, tended to have very few midbodies. Doxsey's group found that when stem cells differentiated, the number of midbodies in the cells decreased. Conversely, when differentiated cells were reprogrammed as induced pluripotent stem cells, midbodies became more prevalent.
The group determined that the accumulation of midbodies in stem cells resulted from the tendency of the organelles to, after division, stick with the cell that has the older centrosome, the cell’s main microtubule organizing center, which is likely to be the stem cell rather than the differentiated daughter cell.
The team also found evidence in culture of multiple midbodies within a variety of cancerous tissues, including HeLa and prostate cancer cells.
“I really think that the midbodies do contribute to the activities of stem cells and cancer cells,” Doxsey told The Scientist. “A big question for the future is, what are the midbodies doing?”
“There could be different possibilities,” said Wieland Huttner, Ettinger's advisor at the Max Planck Institute, whose work has focused on cases when midbodies get released after cell division, something Doxsey's group also witnessed at times. “Our work doesn't necessarily contradict each other.”
“Some cells spit it out, others degrade or keep it. Part of the reason could be cell type specificity,” offered Yukiko Yamashita, a professor at the University of Michigan who did not participate in this research. Either way, Yamashita said, the new data suggest midbodies do have a role in stem cell and cancer cell function.
Doxsey and his colleagues uncovered more details about midbodies' fate within cells by blocking the NBR1 autophagy receptor. They saw that midbody numbers increased, confirming others' findings that midbodies can be degraded via this self-cannibalism mechanism, but now identifying the autophagy receptor.
Additionally, Doxsey's group found that when they inhibited NBR1 by RNA interference, colonies of induced pluripotent stem cells grew more, indicating that they were more efficient at reprogramming. Whether the increased numbers of midbodies are responsible for the change remains to be seen, however. “The possibility remains that other NBR1-linked autophagy targets are responsible for the observed reprogramming,” said Stefan Jentsch, a director at Max Planck Institute of Biochemistry in Martinsried, Germany, in an email.
“Thus the central open question is whether midbody accumulation only correlates with stem cells or whether they actively contribute to stem cell properties,” added Jentsch.
T.-C. Kuo, et al., “Midbody accumulation through evasion of autophagy contributes to cellular reprogramming and tumorigenicity,” Nature Cell Biology, DOI: 10.1038/ncb2332, 2011.