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Stem cells in human bone marrow produce billions of new red blood cells daily, disruption in this process can cause serious disease. Researchers from Charité — Universitätsmedizin Berlin and Harvard Medical School have succeeded in explaining how blood cells are formed. Blood cells develop special types of proteins control the process by which blood-forming stem cells differentiate into different types of blood cells. Patients with Diamond-Blackfan anemia (DBA)-an inherited disorder which disrupts the development of red cells in affected patients, but which does not affect the development of other blood cell types.
Researchers studied the molecular processes involved in the differentiation of stem cells and their development into mature blood cells. They were able to show that a reduction in the number of ribosomes – organelles known as the ‘protein factories’ of the cell is responsible for the disruption in the formation of red blood cells in patients with DBA. The disorder is characterized by mutations affecting one of the protein building blocks of ribosomes. However, while this mutation is responsible for reducing overall levels of these protein factories, it does not affect their composition.
The researchers were also able to show that the process of translating certain sections of genetic information into new proteins is impaired in these ribosomes. Changes affecting the GATA1 transcription factor, a key regulator of red blood cell formation, were evident even at the stem cell stage of development. The parcel of genetic information that is required for the transcription factor’s synthesis, known as messenger RNA, shows specific structural differences. These differences may render it susceptible to the reduction in ribosome levels seen in DBA. The unique structure of the GATA1 messenger RNA may explain why the development from stem cell to blood cell is unaffected in all other types of blood cells.
This basic research study provides an answer to one of the key questions within the field of biology; namely, how the development of blood cell types is regulated after the original genetic information has been transcribed into messenger RNA. The study’s findings show that total ribosome levels work in combination with certain structural elements of messenger RNA to determine the direction of a stem cell’s development and differentiation.
The resultant improved understanding of how Diamond-Blackfan anemia develops may also serve as a basis for the development of new treatments for patients affected by the disorder. The research group is in the process of developing a treatment that specifically targets the GATA1 transcription factor.
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