Haematopoietic stem cells require a highly regulated protein synthesis rate

By Robert A J Signer, Jeffrey A. Magee, A. Salic, S. Morrison. Nature, 2014

607 citations recorded by the source corpus.

Many aspects of cellular physiology remain unstudied in somatic stem cells, for example, there are almost no data on protein synthesis in any somatic stem cell. Here we set out to compare protein synthesis in haematopoietic stem cells (HSCs) and restricted haematopoietic progenitors. We found that the amount of protein synthesized per hour in HSCs in vivo was lower than in most other haematopoietic cells, even if we controlled for differences in cell cycle status or forced HSCs to undergo self-renewing divisions. Reduced ribosome function in Rpl24Bst/+ mice further reduced protein synthesis in HSCs and impaired HSC function. Pten deletion increased protein synthesis in HSCs but also reduced HSC function. Rpl24Bst/+ cell-autonomously rescued the effects of Pten deletion in HSCs; blocking the increase in protein synthesis, restoring HSC function, and delaying leukaemogenesis. Pten deficiency thus depletes HSCs and promotes leukaemia partly by increasing protein synthesis. Either increased or decreased protein synthesis impairs HSC function.

Subfields: Hematology, Public Health, Environmental and Occupational Health

View Paper: https://www.semanticscholar.org/paper/78a99942d05d6493c61911b7af93ecae87d80bc5

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In Public Health, Environmental and Occupational Health

1. Guo-li Ming
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Citations in the corpus

• Tumorigenic and Immunosuppressive Effects of Endoplasmic Reticulum Stress in Cancer (2017, unknown): “Similarly, oncogenic transformation driven by loss of the tumor suppressors p53, PTEN, TSC1 or TSC2 dramatically enhances protein synthesis rates, leading to ER stress (Hart et al., 2012; Namba et al., 2015; Signer et al., 2014).”
• Single-Cell Transcriptomics Reveals a Population of Dormant Neural Stem Cells that Become Activated upon Brain Injury. (2015, unknown): “The requirement of a tight regulation of global protein translation in stem cell function has been previously reported for hematopoietic stem cells (Signer et al., 2014).”
• Single-cell RNA-seq with Waterfall Reveals Molecular Cascades underlying Adult Neurogenesis (2015, background): “…(Figures 6C and S6D), suggesting a possible demarcation of G0 to G1 transition and providing the timing for switches in protein synthesis, the regulation of which is important for tem Cell 17, 360–372, September 3, 2015 ª2015 Elsevier Inc. 369 somatic stem cell function (Signer et al., 2014).”