Ribosomes Play A Role in the Mechanism of Blood Cell Differentiation

Low ribosome levels in DB anemia affects blood cell differentiation.

Source: https://www.cell.com/cell/fulltext/S0092-8674(18)30213-7

Research Highlights

  • Diamond-Blackfan anemia (DB anemia) is a unique blood disorder where red blood cell precursors and progenitors are selectively reduced in the bone marrow of patients, while all other lineages are apparently produced normally.
  • Molecular lesions underlying DB anemia reduce the number of ribosomes in hematopoietic cells.
  • Ribosome composition remains constant in cells with DB anemia-associated lesions.
  • Low ribosome count selectively and negatively affects the translation of a part of messenger RNAs.
  • Translational disturbances in DB anemia impair lineage development in hematopoietic stem and progenitor cells.

Blood cell production is thought to occur through an order of differentiation steps. Some studies have shown that the cell production may occur earlier in hematopoietic stem and progenitor cells. The relationship between human blood diseases and the mechanism of these cell productions remain poorly understood. By studying a genetic blood disorder, Diamond-Blackfan anemia (DB anemia), where the majority of mutations affect proteins in ribosomes and the red blood cell production is selectively disturbed, the study is able to give light on information about the mechanism on how lineage commitment is produced normally and disrupted by the disease. The research shows that in DB anemia, the amount of ribosomes is low, while ribosome composition remains constant. The reduction in ribosome levels extremely alters translation of a select part of messenger RNAs. The study shows how the reduced translation of select RNA transcripts in hematopoietic stem and progenitor cells can impair the development of red blood cells, lighting up a regulatory role for ribosome levels in cell differentiation.



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