The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
The Lkb1 metabolic sensor maintains haematopoietic stem cell survival
Open accessAbstract
Haematopoietic stem cells (HSCs) can convert between growth states that have marked differences in bioenergetic needs. Although often quiescent in adults, these cells become proliferative upon physiological demand. Balancing HSC energetics in response to nutrient availability and growth state is poorly understood, yet essential for the dynamism of the haematopoietic system. Here we show that the Lkb1 tumour suppressor is critical for the maintenance of energy homeostasis in haematopoietic cells. Lkb1 inactivation in adult mice causes loss of HSC quiescence followed by rapid depletion of all haematopoietic subpopulations. Lkb1-deficient bone marrow cells exhibit mitochondrial defects, alterations in lipid and nucleotide metabolism, and depletion of cellular ATP. The haematopoietic effects are largely independent of Lkb1 regulation of AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) signalling. Instead, these data define a central role for Lkb1 in restricting HSC entry into cell cycle and in broadly maintaining energy homeostasis in haematopoietic cells through a novel metabolic checkpoint.
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Cites
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Restoration of p53 function leads to tumour regression in vivo
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Cited by
Mechanism and medical implications of mammalian autophagy
Dikic, I., & Elazar, Z. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0003-4 · Cited by 2,771
RNA sequencing: advances, challenges and opportunities
Ozsolak, F., & Milos, P. M. (2011) · Nature Reviews Genetics · doi:10.1038/nrg2934 · Cited by 2,135
“The first massively parallel DRS approach was recently developed using the Helicos single-molecule sequencing platfor”
MethodSelf-citationMolecular regulation of stem cell quiescence
Cheung, T. H., & Rando, T. A. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3591 · Cited by 1,148
Regulation and function of mTOR signalling in T cell fate decisions
Chi, H. (2012) · Nature Reviews Immunology · doi:10.1038/nri3198 · Cited by 1,035
Metabolic requirements for the maintenance of self-renewing stem cells
Ito, K., & Suda, T. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3772 · Cited by 1,014
Metadata
- Authors
- Gurumurthy, S., Xie, S. Z., Alagesan, B., Kim, J., Yusuf, R. Z., Saez, B., Tzatsos, A., Ozsolak, F., Milos, P., Ferrari, F., Park, P. J., Shirihai, O. S., Scadden, D. T., & Bardeesy, N.
- Venue
- Nature
- Published
- 2010-12-01
- Volume
- 468
- Issue
- 7324
- Pages
- 659-663
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2055309955
- Cited by
- 391
- References
- 37
- FWCI
- 21.19
- Type
- journal article
- Language
- en
- Open access
- green
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- Gurumurthy, S., Xie, S. Z., Alagesan, B., Kim, J., Yusuf, R. Z., Saez, B., Tzatsos, A., Ozsolak, F., Milos, P., Ferrari, F., Park, P. J., Shirihai, O. S., Scadden, D. T., & Bardeesy, N. (2010). The Lkb1 metabolic sensor maintains haematopoietic stem cell survival. Nature. https://doi.org/10.1038/nature09572
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