Proteins’ role in red blood cell production underestimated—until now
Posted on Tuesday, May 26, 2020
By Michelle Read
Imagine compensating for shortages in blood donations by growing blood in a lab. Or, discovering a way for those with blood diseases to regenerate their own stores of blood.
These are some of the exciting implications behind new findings out of the Marjorie Brand lab at the University of uOttawa Faculty of Medicine, published in their recent paper in Molecular Cell.
The study reveals new principles of gene regulation in erythropoiesis (the production of red blood cells), as well as a more accurate technique for exploring cell fate and a new model for researchers to follow—big news for anyone studying how a stem cell decides to become a red blood cell.
“Our work has important implications in the study of blood diseases, lab-grown blood and more,” says Dr. Brand, a professor in the Department of Medicine and a senior scientist at The Ottawa Hospital.
The team studied over a hundred cellular factors that direct human hematopoietic stem cells to become red blood cells. According to Dr. Brand, it was the first time those factors were studied at the protein level, which they did by scaling up a mass spectrometry technique called ‘selected reaction monitoring’ to unprecedented levels.
The researchers pinpointed how many copies of each protein every human hematopoietic stem cell contains, and determined how the quantities of those proteins change during the formation of red blood cells. Compared to techniques previously used to explore cell fate, says Dr. Brand, the study of proteins is a more accurate predictor of cell fate.
“Our paper tells the community how many of each protein must be present in a blood stem cell for it to work properly,” she explains. “It also implies that a stem cell without those numbers of proteins may not work properly.”
Co-author Dr. Ted Perkins, associate professor in BMI and cross-appointed to the School of Information Technology and Engineering, applied mathematical modeling to these protein numbers.
In doing so, the team mapped the first gene regulatory network—interconnected pathways of genes being turned on and off by proteins in a stem cell to help it decide what it will become.
“Understanding how a stem cell decides to become a red blood cell can help decipher what goes wrong in diseases where the production of blood cells does not work, such as anemia and even cancer,” says Dr. Brand.