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Cell DOI:10.1016/j.cell.2018.02.036

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

Publication TypeJournal Article
Year of Publication2018
AuthorsKhajuria, 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
JournalCell
Volume173
Issue1
Pages90-103.e19
Date Published2018 Mar 22
ISSN1097-4172
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.

DOI10.1016/j.cell.2018.02.036
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/29551269?dopt=Abstract

Alternate JournalCell
PubMed ID29551269
PubMed Central IDPMC5866246
Grant ListR01 DK103794 / DK / NIDDK NIH HHS / United States
R33 HL120791 / HL / NHLBI NIH HHS / United States
T32 HL007574 / HL / NHLBI NIH HHS / United States
Additional Materials