Datasets

Title	Consequences of Ribosomal Protein Haploinsufficiency in Human Hematopoiesis
Organism
Number of Samples	6
Release Date	2016/10/25 00:00
Sequencing Types
Protocol Details

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Title
Authors	Khajuria RK,Munschauer M,Ulirsch JC,Fiorini C,Ludwig LS,McFarland SK,Abdulhay NJ,Specht H,Keshishian H,Mani DR,Jovanovic M,Ellis SR,Fulco CP,Engreitz JM,Schütz S,Lian J,Gripp KW,Weinberg OK,Pinkus GS,Gehrke L,Regev A,Lander ES,Gazda HT,Lee WY,Panse VG,Carr SA,Sankaran VG
Journal	Cell
Publication Date	2018 Mar 22
Abstract	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. Copyright © 2018 Elsevier Inc. All rights reserved.
PMC	PMC5866246
PMID	29551269
DOI

Khajuria et al. 2018 (PRJNA350543)