Ribosome Levels Selectively Regulate Translation and Lineage Commitment in Human Hematopoiesis.

Published on Mar 1, 2018in Cell36.216
· DOI :10.1016/j.cell.2018.02.036
Rajiv K. Khajuria4
Estimated H-index: 4
Mathias Munschauer12
Estimated H-index: 12
(Broad Institute)
+ 24 AuthorsVijay G. Sankaran33
Estimated H-index: 33
(Broad Institute)
Summary Blood cell formation is classically thought to occur through a hierarchical differentiation process, although recent studies have shown that lineage commitment may occur earlier in hematopoietic stem and progenitor cells (HSPCs). The relevance to human blood diseases and the underlying regulation of these refined models remain poorly understood. By studying a genetic blood disorder, Diamond-Blackfan anemia (DBA), where the majority of mutations affect ribosomal proteins and the erythroid lineage is selectively perturbed, we are able to gain mechanistic insight into how lineage commitment is programmed normally and disrupted in disease. We show that in DBA, the pool of available ribosomes is limited, while ribosome composition remains constant. Surprisingly, this global reduction in ribosome levels more profoundly alters translation of a select subset of transcripts. We show how the reduced translation of select transcripts in HSPCs can impair erythroid lineage commitment, illuminating a regulatory role for ribosome levels in cellular differentiation.
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