Signalling specialisation
Hematopoietic stem cells specifically turn on and off different genes in response to external signalling molecules.
Most organs in the human body are maintained by a type of immature cells known as adult stem cells, which ensure a constant supply of new, mature cells. Adult stem cells monitor their environment through external signalling molecules and replace damaged cells as needed.
Stem cell therapy takes advantage of the regenerative ability of immature stem cells and can be helpful for conditions such as blood diseases, autoimmune diseases, neurodegeneration and cancer. For example, hematopoietic stem-cell transplantation is a treatment for some types of cancer and blood disorders, in which stem cells are harvested from the blood or bone marrow and reintroduced into the body, where they can develop into all types of blood cells, including white blood cells, red blood cells and platelets.
Hematopoietic stem-cell transplants have been in use for over 30 years, but they remain a highly risky procedure. One of the challenges is that outcomes can vary between patients and many of the factors that can influence the ‘regenerative’ potential of hematopoietic stem cells, such as external signalling molecules, are not well understood.
To fill this gap, Fast et al. analysed which genes are turned on and off in hematopoietic stem cells in response to several external signalling molecules. To do so, three signalling pathways in mice were altered by injecting them with different chemicals. After two hours, the hematopoietic stem cells were purified and the gene expression for each cell was analysed.
This revealed that the types of genes and the strength at which they were affected by each chemical was unique. Moreover, hematopoietic stem cells responded rapidly to external signals, with substantial differences in gene expression between individual groups of cells. Contrary to more specialised cells, the external signalling genes in some hematopoietic stem cells were already activated without being injected with external signalling molecules. This suggest that low levels of external signalling molecules released from their microenvironment may prepare stem cells to better respond to future stress or injuries.
These results help to better understand stem cells and to evaluate how the signalling state of hematopoietic stem cells affects regeneration, and ultimately improve hematopoietic stem cell transplantation for patients.
Originally published at https://elifesciences.org/digests/66512.
