Stem Cell to Blood Cell Process Uncovered

Previously undetected steps in the process from stem cell to blood cell have just been discovered, and the process has been labeled haematopoiesis. Involved a highly complex series of events that determine the face of closely related populations of blood progenitor cells, the discovery was made during an international collaboration study, co-authored by The University of Western Australia's School of Pathology and Laboratory Medicine's Head  Professor Wendy Erber.

The study, which is part of the large international BLUEPRINT research project to understand blood disorders, identified thousands of differences in gene expression between blood cell types. These differences result from many specific events that are crucial for normal blood development. Errors in this process can lead to blood disorders including leukaemia.

For the first time, a comprehensive catalogue of transcription factors and other proteins that regulate this sophisticated process has been generated. This research has discovered the extent to which the RNA is cut and pasted together in different ways during haematopoiesis leading to specific forms of proteins for each of these stages. Until this study, haematopoiesis was relatively well understood at the level of DNA. What was not known was how the genetic information in DNA was then transcribed to generate RNA, leading to protein formation.

The University of Cambridge's Experimental Haematology Professor Willem Ouwehand said, “We have identified thousands of novel places where the RNA is processed in an alternative way".

The critical importance of the alternative splicing of RNA in blood cell development was illustrated by studying the role of two different forms of the same transcription factor in the formation of megakaryocytes, the progenitor cell for blood platelets.

“Such events changed the amount, structure and behaviour of proteins derived from a single gene. Alternative proteins could drive stem cells towards becoming different mature blood cells,” Professor Erber said.

Professor Erber also said that the hematopoietic stem cells and other cells needed for this study had not previously been studied in great detail because they are extremely rare in the bone marrow of adults.

“In this study we were able to purify the cells from umbilical cord blood donations, where the concentration of these progenitor cells is surprisingly high.”

The results of this study have significant applications for patients with blood disorders. Scientists can begin to design diagnostics and new therapies for blood disorders including leukaemia. They will be of great value in future studies in stem cell transplantation therapy, regenerative medicine and discovering the genetic basis of rare inherited haematological and immunological disorders