Identifying a mechanism for forming blood stem cells

Scientists from the Garvan Institute of Medical Research and Monash University have uncovered a mechanism essential for forming hematopoietic stem cells (HSCs) - a special group of cells in the early embryo that ultimately generate all the blood and immune cells in our bodies. Their research has been published in the journal Nature.

Dr Georgina Hollway from the Garvan Institute, along with Dr Phong Dang Nguyen and Professor Peter Currie from the Australian Regenerative Medicine Institute (ARMI), made their discovery when they were researching a zebra fish muscle mutant. They noticed that muscle-deficient zebra fish, which have a deficit of muscle stem cells, have several times the normal population of hematopoietic stem cells.

Dr Georgina Hollway, surrounded by zebra fish.

They identified a novel gene (meox1) that acts like a molecular switch in a compartment of the embryo known as the somite. The gene’s level of expression determines the fate of the two groups of stem cells in equal and opposite ways. Low levels of meox1 mean less muscle and more blood stem cells. High levels of meox1 mean more muscle and less blood stem cells.

It was already known that HSCs form in the dorsal aorta - the earliest-forming blood vessel in the embryo - and not in the somite, and so the research team couldn’t understand the connection between the regions. They eventually identified a novel group of cells in the somite, called endotome cells, which migrate to the adjacent dorsal aorta and send molecular signals to induce nascent HSCs.

“Endotome cells act like a comfy sofa for pre-HSCs to snuggle into, helping them progress to become fully fledged stem cells,” Professor Currie said. “Not only did we identify some of the cells and signals required for HSC formation; we also pinpointed the genes required for endotome formation in the first place.”

According to Dr Hollway, “This is a significant finding because it takes us one step closer to being able to make blood stem cells in the laboratory” - an achievement which would be “critically important”, said Professor Currie.

“The problem we currently face is getting enough of these stem cells so we can generate any blood cell type from them,” Professor Currie said. “Using regenerative medicine, and in particular inducing them from embryonic stem cells, or from induced pluripotent stem cells, has been very hard to do.

“We need to better understand the genetic factors, or signals, that are required to make a hematopoietic stem cell from a pluripotent cell. We believe that the new group of cells we’ve identified in the somite are an important piece of that puzzle.”