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We are analyzing https://www.nature.com/articles/nature13035.

Title:
Haematopoietic stem cells require a highly regulated protein synthesis rate | Nature
Description:
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. Haematopoietic stem cells (HSCs) have a lower rate of protein synthesis in vivo than most other haematopoietic cells, and both increases and decreases in the rate of protein synthesis impair HSC function, demonstrating that HSC maintenance—and hence, cellular homeostasis—requires the rate of protein synthesis to be highly regulated. In the absence of data to the contrary, it has been widely assumed that protein synthesis is a routine function performed similarly in most cells. The availability of a technique for quantifying rates of protein synthesis in vivo in mice, based on the administration of a puromycin analogue OP-Puro, means that that notion can now be tested. Sean Morrison and colleagues use this method, combined with flow cytometry, to study protein synthesis in individual haematopoietic stem cells (HSCs). They find that HSCs have lower rates of protein synthesized per hour than do most other haematopoietic cell types. Genetic approaches show that both increased and decreased rates of protein synthesis impair HSC function. This work suggests that HSC maintenance depends upon a highly regulated rate of protein synthesis, and that maintenance of appropriate levels of protein synthesis can be critical for cellular homeostasis.
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cells, pubmed, article, mice, cell, google, scholar, cas, protein, stem, nature, hscs, synthesis, experiments, data, rplbst, independent, marrow, central, bone, oppuro, haematopoietic, wildtype, fig, content, ads, vivo, relative, treated, statistical, hematopoietic, blood, extended, administration, treatment, significance, control, population, performed, total, function, differences, pten, access, cancer, assess, morrison, hsc, usa, represent,

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nature portfolio permissions reprints privacy policy advertising research institute content cell-type-specific quantification health research social media author information authors cd4−cd8−cd44+cd25− cd4−cd8−cd44+cd25+ cd4−cd8−cd44−cd25+ cd4−cd8−cd44-cd25− author correspondence cd71+ter119+ erythroid progenitors system-level model reveals nature rev nature methods 6 pten-loss-evoked leukemogenesis cd150+cd48−lsk cells nature med puromycin analogue op-puro rpl24bst/+ cell-autonomously rescued cd150+cd48-lsk hscs springerlink instant access highly regulated rate early t-lineage progenitor nature 456 nature 485 nature 441 nature 453 nature 489 nature 404 nature 509 nature permissions bone marrow failure hematopoietic stem cell human hematopoietic stem haematopoietic-cell populations relative donor-cell engraftment levels hematopoietic stem cells development 131 development proteotoxic stress conditions op-puro fluorescence ribosomal protein haploinsufficiency extended data figures p53 protein family op-puro reagent

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      headline:Haematopoietic stem cells require a highly regulated protein synthesis rate
      description: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. Haematopoietic stem cells (HSCs) have a lower rate of protein synthesis in vivo than most other haematopoietic cells, and both increases and decreases in the rate of protein synthesis impair HSC function, demonstrating that HSC maintenance—and hence, cellular homeostasis—requires the rate of protein synthesis to be highly regulated. In the absence of data to the contrary, it has been widely assumed that protein synthesis is a routine function performed similarly in most cells. The availability of a technique for quantifying rates of protein synthesis in vivo in mice, based on the administration of a puromycin analogue OP-Puro, means that that notion can now be tested. Sean Morrison and colleagues use this method, combined with flow cytometry, to study protein synthesis in individual haematopoietic stem cells (HSCs). They find that HSCs have lower rates of protein synthesized per hour than do most other haematopoietic cell types. Genetic approaches show that both increased and decreased rates of protein synthesis impair HSC function. This work suggests that HSC maintenance depends upon a highly regulated rate of protein synthesis, and that maintenance of appropriate levels of protein synthesis can be critical for cellular homeostasis.
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