Putting the “Brakes” on Adult Blood Stem Cell Proliferation
A recent study revealed a natural process that limits the ability of adult blood stem cells to proliferate (i.e., divide to increase their numbers). The body’s adult blood stem cells are able to replace blood cells damaged by disease, injury, or age. These cells can be found in either a state of quiescence or of proliferation. Previous research has shown that the transition from quiescence to the proliferative state requires the action of cellular structures called mitochondria, which take chemical energy from sugars and fats and convert it into fuel that is usable throughout the cell.
Recently, researchers reported that during proliferative growth the mitochondria of adult blood stem cells from both female and male mice accumulate defects that limit their ability to convert food energy into cellular fuel. When the cells return to their quiescent state, the resulting dysfunctional mitochondria are not repaired. Rather, their accumulation serves as a sort of record of each cell’s replicative history. The researchers found that the mitochondrial defects result from loss of a protein called Drp1 that functions as part of the proliferative machinery. With each round of proliferative growth, Drp1 loss therefore reduces the capacity of the blood stem cells to undergo future rounds of cell division. This phenomenon may effectively be an intrinsic “safety feature,” limiting the cells’ ability to proliferate excessively. Since such unchecked cell division can lead to cancer, understanding this process could one day lead to improved methods for prevention or treatment of cancers. In addition, this research may help in the development of therapies that overcome the limits on adult blood stem cell proliferation in a selective fashion, allowing regeneration of critical blood cells that might otherwise be irrevocably lost through disease or injury.
Hinge A, He J, Bartram J,…Filippi MD. Asymmetrically segregated mitochondria provide cellular memory of hematopoietic stem cell replicative history and drive HSC attrition. Cell Stem Cell 26: 420-430, 2020.