A recent study led by the Spanish IMIM (Hospital del Mar Medical Research Institute) shows that the strength and efficiency of an activated protein called Notch (participating at different stages of embryonic development), determines the fate of cells, that is, to decide whether cells will form the aortic or hematopoietic stem cells. For arterial cells, a lot of Notch molecules need to be activated, but for hematopoietic cells, the need will be less. Research results were published in Nature Communications.
According to Dr. Anna Bigas, the stem cell and cancer research group leader of IMIM, they’ve proven that, in order to achieve these levels of activation, there is a competitive relationship between the two proteins which activate Notch molecules, namely, one ligand will limit the activation generated by another to form hematopoietic stem cells.
So far we have known that, due to the study of this team and other people, the Notch activation for the formation of arterial and hematopoietic stem cells is essential. It is also clear that the protein ligands responsible for the activation are Delta4 and Jagged1. In the paper, researchers have shown how the signals, in order to achieve a certain level of activation, form the two different types of cells.
The signal that is essential for the preparation of hematopoietic stem cells in the laboratory is quite important, whether using embryonic stem cells or other sources. At present, stem cells are obtained from the laboratory, with the characteristics of stem cells, but the process is still not very effective or reproducible. This study will help to improve the quality and efficiency of hematopoietic stem cells, which could mean that in the future, many patients with no compatible donor, will obtain the appropriate organ transplant.
The researchers used mouse cells to carry out the study. The next step would be to repeat the study by using human embryonic stem cells or programmed vascular endothelial cells. The researchers believe that it will work in a similar way. In addition, it is possible to produce other types of cells with the very similar mechanism.
The researchers concluded that although this is not immediately applicable, and not all signals are known and we also do not know how to adjust them, we are gradually drafting a more precise program to learn how to generate portable cell.
Notch signal strength controls cell fate in the haemogenic endothelium, Nature Communications.