Red blood cells are the most abundant cells in the human body, and transport oxygen and carbon dioxide. Millions of people worldwide suffer from anaemia, a condition in which the patient has an insufficient amount of red blood cells. Patients with chronic anaemia are among the most problematic cases. They receive regular blood transfusions from different donors, which can eventually lead to the patient developing a reaction to the new blood. They simply become allergic to the donor’s blood.

Therefore, finding a way to make blood from an individual’s own skin cells would bring relief to this group of patients.  Now, a study from researchers at Lund University and the Center of Regenerative Medicine successfully identifies the four genetic keys that unlock the genetic code of skin cells, to reprogram them to start producing red blood cells instead.  The team state that this is the first time anyone has ever succeeded in transforming skin cells into red blood cells, which is incredibly exciting.  The opensource study is published in the journal Cell Reports.

Previous studies show that every individual has a unique genetic code, which is a complete instruction manual describing exactly how all the cells in the body are formed. This instruction manual is stored in the form of a specific DNA sequence in the cell nucleus. All human cells, brain, muscle, fat, bone and skin cells, have the exact same code. The thing that distinguishes the cells is which chapter of the manual the cells are able to read.  Although several factors are known to participate in the conserved genetic program instructing development of committed erythroid progenitors, the minimal combination of factors required for direct induction of red blood cell fate remains unknown.  The current study investigates how cells open the chapter that contains instructions on how to produce red blood cells.

The current study utilises mice to show that it is also possible to reprogram skin cells from humans into red blood cells.  Results show that out of 20,000 genes, only four are necessary to reprogram skin cells to start producing red blood cells, with all four are necessary in order for it to work.  Data findings show that the transcription factors Gata1, Tal1, Lmo2, and c-Myc (GTLM) as the minimal set of factors for direct conversion of mouse and human fibroblasts into erythroid progenitors

The lab state that with the help of a retrovirus, they introduced different combinations of over 60 genes into the skin cells’ genome, until they successfully converted the skin cells into red blood cells.  They go on to add that the resulting cells, which they term induced erythroid progenitors/precursors (iEPs), resemble bona fide erythroid cells in terms of morphology, colony-forming capacity, and gene expression.

The group also observed that while murine GTLM iEPs express both embryonic and adult globin genes, the addition of Klf1 or Myb induces a switch in globin gene expression to generate iEPs with a predominant definitive-type globin expression pattern. They go on to conclude that further studies on how the generated blood performs in living organisms are needed.

The team surmise that their findings are significant for understanding how red blood cells are produced and which genetic instructions they require, creating an opportunity to produce red blood cells from the skin cells of a patient.  For the future, the researchers state that the GTLM factors could potentially be used to enhance methods for in vitro production of red blood cells for personalized transfusion medicine.

Source: Lund University