Yale Scientists Unlock “Sugar Code” to Regulate in vivo and ex-vivo Blood Stem Cell Production
Yale scientists have identified a crucial biological link in the process that transforms certain complex sugars into hematopoietic stem and progenitor cells.
Reprogramming cells into hematopoietic stem and progenitor cells (HSPCs) has been the holy grail for autologous stem cells transplants, a lifesaving therapy for blood cancer diseases. However, the mechanisms that regulate this transition at the cellular and molecular level are poorly understood. A new study published in Science identifies microRNA (miR)-223 as a crucial link between complex sugars called glycans and endothelial-to-hematopoietic transition (EHT), a process where hemogenic endothelium differentiates into hematopoietic stem and progenitor cells (HSPCs).
A breakthrough in stem cell transplantation occurred in the 1960s when biologist Ernest McCulloch, MD and biophysicist James Till, PhD discovered that hematopoietic stem cells (HSCs) have the ability to self-renew and eventually produce different types of blood cells. These stem cells can form all blood cell lineages needed throughout life.
A second milestone was the discovery of biomolecules made from sugar. Specific cell surface glycans play an important role in human biology from how our body recognizes and fights disease to cell cycle progression.
“The progress made toward reprograming cells in the past five years has been based on studies that elucidate the mechanisms of developmental hematopoiesis, where blood stem cells are naturally born from bona fide aortic endothelial cells via an endothelial to hematopoietic transition. This transition from endothelial cells to blood stem cells is highly regulated and restricted to a small portion of endothelial cells during a brief period of time,” said Stefania Nicoli, PhD, associate professor of cardiovascular medicine and genetics and senior author of the study.
