Researchers from the University of Wisconsin-Madison have identified two groups of regulatory proteins that are responsible for directing stem cells to become different types of blood cell. The research not only sheds light on the factors responsible for the production of blood cells very early in development, but it could eventually lead to a safe method for the generation of large quantities of any kind of blood cell in the lab, which would have vast therapeutic potential. The study has been published in Nature Communications.
Hematopoietic stem cells are progenitor cells that are capable of giving rise to all types of blood cell. As the embryo develops, these are produced from a unique population of cells called hemogenic endothelial cells. These cells are found in only a small number of sites in the developing embryo and only for a very short period of time. While this much was known, scientists knew little about the regulatory factors that governed this process until now.
The researchers investigated the effects of 27 different candidate factors on stem cells and found that just two groups of regulatory proteins could induce different blood cell programs from human pluripotent stem cells (hPSCs). hPSCs are unspecialized cells that have the potential to develop into other, specialized cell types such as blood cells or cells of the nervous system.
The regulators identified were proteins called transcription factors; these are cellular proteins that are capable of changing the expression of genes by altering a process called transcription. Transcription is the process of converting our genetic material, DNA, into RNA which is then used as a template to produce proteins.
They found that these transcription factors were capable of giving rise to a range of blood cells including red blood cells and different types of white blood cell. Furthermore, by boosting the levels of these two transcription factors in hPSCs in the lab, the researchers were able to closely replicate the sequence of events observed in the developing embryo. They did this by overexpressing modified mRNA; mRNA is the blueprint message used in the production of proteins. Because this does not involve altering the DNA sequence itself, for example with a virus, the technique is safer than some other methods.
Using this particular method, the researchers were able to produce copious amounts of blood cells. For every 1 million stem cells used, they could produce 30 million blood cells.
“This is the first demonstration of the production of different kinds of cells from human pluripotent stem cells using transcription factors,” said lead researcher Igor Slukvin in a news-release.
The researchers believe that this novel and efficient approach may be applicable to the production of other types of cell with therapeutic potential, for example heart or pancreatic cells.
While this is an encouraging step forward in the field, the researchers have so far been unable to produce hematopoietic stem cells, a significant challenge in this field. These cells are used in the treatment of certain cancers, such as leukemia, and various blood disorders.