@article{9448a337f08a48baaa99b7b65e17a4bd,
title = "Haematopoietic stem cells require a highly regulated protein synthesis rate",
abstract = "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.",
author = "Signer, {Robert A.J.} and Magee, {Jeffrey A.} and Adrian Salic and Morrison, {Sean J.}",
note = "Funding Information: Acknowledgements S.J.M. is a Howard Hughes Medical Institute Investigator, the Mary McDermott Cook Chair in Pediatric Genetics, and the director of the Hamon Laboratory for Stem Cells and Cancer. This work was supported by the Cancer Prevention and Research Institute of Texas and the National Institute on Aging (R37 AG024945). R.A.J.S. was supported by fellowships from the Leukemia & Lymphoma Society (5541-11) and the Canadian Institutes of Health Research (MFE-106993). J.A.M. was supported by the UT Southwestern K12 Pediatrics Training Grant (K12-HD068369). We thank A. Pineda, K. Cowan, E. Daniel, M. Acar, H. Oguro, J. Peyer, K. Rajagopalan, M. Agathocleous and E. Piskounova for technical support and advice; N. Loof and the Moody Foundation Flow Cytometry Facility, L. Hynan and J. Reisch for advice regarding statistics; J. Shelton for histology; and R. Coolon, S. Manning, M. Gross and K. Correll for mouse colony management.",
year = "2014",
doi = "10.1038/nature13035",
language = "English",
volume = "508",
pages = "49--54",
journal = "Nature",
issn = "0028-0836",
number = "7498",
}