The blood stem cells that live in bone marrow are at the top of a complex family tree. Such stem cells split and divide down various pathways that ultimately produce red cells, white cells, and platelets. These “daughter” cells must be produced at a rate of about 1 million per second to constantly replenish the body’s blood supply.
Researchers have long wondered what allows these stem cells to persist for decades, when their progeny last for days, weeks, or months before they need to be replaced. A new study led by Dennis Discher, the Robert D. Bent Professor in the School of Engineering and Applied Science, has uncovered one of the mechanisms that allow these stem cells to keep dividing in perpetuity.
“Your blood cells are constantly getting worn out and replaced,” Discher says. “We want to understand how the stem cells responsible for making these cells can last for decades without being exhausted.”
The researchers found that a form of the motor protein that allows muscles to contract helps these cells divide asymmetrically, so that one part remains a stem cell while the other becomes a daughter cell.
Looking to identify the forces responsible for this phenomenon, the researchers analyzed all of the genes expressed in the stem cells and their more rapidly dividing progeny. Proteins that only went to one side of the dividing cell, the researchers thought, might play a role in partitioning other key factors responsible for keeping one side a stem cell.
They saw different expression patterns of the motor protein myosin II, which has two forms, A and B. Myosin II is the protein that enables the body’s muscles to contract, but in non-muscle cells it is also used in cell division, where it helps cleave and close off the cell walls as the cell splits apart.
The researchers discovered that the stem cell has both types of myosin but their progeny only have the A form. Inferring that the B form was the key, the researchers labeled the proteins in dividing stem cells with different colors and put them under the microscope.
“We could see that the myosin IIB goes to one side of the dividing cell, which causes it to cleave differently,” Discher says. ”It’s like a tug of war, and the side with the B pulls harder and stays a stem cell.”
Their findings could provide new insight into blood cancers, such as leukemia, and eventually lead to ways of growing transfusable blood cells in a lab.