The Lkb1 metabolic sensor maintains haematopoietic stem cell survival

Tothova, Z. & Gilliland, D. G. FoxO transcription factors and stem cell homeostasis: insights from the hematopoietic system. Cell Stem Cell 1, 140–152 (2007)

Gan, B. et al. mTORC1-dependent and -independent regulation of stem cell renewal, differentiation, and mobilization. Proc. Natl Acad. Sci. USA 105, 19384–19389 (2008)

Ito, K. et al. Regulation of reactive oxygen species by Atm is essential for proper response to DNA double-strand breaks in lymphocytes. J. Immunol. 178, 103–110 (2007)

Liu, J. et al. Bmi1 regulates mitochondrial function and the DNA damage response pathway. Nature 459, 387–392 (2009)

Chen, C. et al. TSC-mTOR maintains quiescence and function of hematopoietic stem cells by repressing mitochondrial biogenesis and reactive oxygen species. J. Exp. Med. 205, 2397–2408 (2008)

Shackelford, D. B. & Shaw, R. J. The LKB1-AMPK pathway: metabolism and growth control in tumour suppression. Nature Rev. Cancer 9, 563–575 (2009)

Shaw, R. J. et al. The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress. Proc. Natl Acad. Sci. USA 101, 3329–3335 (2004)

Hawley, S. A. et al. Complexes between the LKB1 tumor suppressor, STRADα/β and MO25α/β are upstream kinases in the AMP-activated protein kinase cascade. J. Biol. 2, 28 (2003)

Hardie, D. G. AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nature Rev. Mol. Cell Biol. 8, 774–785 (2007)

Narbonne, P. & Roy, R. Caenorhabditis elegans dauers need LKB1/AMPK to ration lipid reserves and ensure long-term survival. Nature 457, 210–214 (2009)

Lizcano, J. M. et al. LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK//PAR-1. EMBO J. 23, 833–843 (2004)

Kiel, M. J. et al. SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell 121, 1109–1121 (2005)

Bardeesy, N. et al. Loss of the Lkb1 tumour suppressor provokes intestinal polyposis but resistance to transformation. Nature 419, 162–167 (2002)

Kuhn, R., Schwenk, F., Aguet, M. & Rajewsky, K. Inducible gene targeting in mice. Science 269, 1427–1429 (1995)

Chan, I. T. et al. Conditional expression of oncogenic K-ras from its endogenous promoter induces a myeloproliferative disease. J. Clin. Invest. 113, 528–538 (2004)

Torchia, E. C., Boyd, K., Rehg, J. E., Qu, C. & Baker, S. J. EWS/FLI-1 induces rapid onset of myeloid/erythroid leukemia in mice. Mol. Cell. Biol. 27, 7918–7934 (2007)

Essers, M. A. G. et al. IFNα activates dormant haematopoietic stem cells in vivo . Nature 458, 904–908 (2009)

Maiuri, M. C., Zalckvar, E., Kimchi, A. & Kroemer, G. Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nature Rev. Mol. Cell Biol. 8, 741–752 (2007)

Ichimura, Y. et al. A ubiquitin-like system mediates protein lipidation. Nature 408, 488–492 (2000)

Shaw, R. J. et al. The LKB1 tumor suppressor negatively regulates mTOR signaling. Cancer Cell 6, 91–99 (2004)

Corradetti, M. N., Inoki, K., Bardeesy, N., DePinho, R. A. & Guan, K. L. Regulation of the TSC pathway by LKB1: evidence of a molecular link between tuberous sclerosis complex and Peutz-Jeghers syndrome. Genes Dev. 18, 1533–1538 (2004)

Shaw, R. J. et al. The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science 310, 1642–1646 (2005)

Koh, H. J. et al. Skeletal muscle-selective knockout of LKB1 increases insulin sensitivity, improves glucose homeostasis, and decreases TRB3. Mol. Cell. Biol. 26, 8217–8227 (2006)

Koh, H. J. et al. Sucrose nonfermenting AMPK-related kinase (SNARK) mediates contraction-stimulated glucose transport in mouse skeletal muscle. Proc. Natl Acad. Sci. USA 10.1073/pnas.1008131107 (16 August 2010)

Gurumurthy, S. et al. LKB1 deficiency sensitizes mice to carcinogen-induced tumorigenesis. Cancer Res. 68, 55–63 (2008)

Contreras, C. M. et al. Loss of Lkb1 provokes highly invasive endometrial adenocarcinomas. Cancer Res. 68, 759–766 (2008)

Hezel, A. F. et al. Pancreatic LKB1 deletion leads to acinar polarity defects and cystic neoplasms. Mol. Cell. Biol. 28, 2414–2425 (2008)

Sanchez-Cespedes, M. A role for LKB1 gene in human cancer beyond the Peutz-Jeghers syndrome. Oncogene 26, 7825–7832 (2007)

Klimova, T. A. et al. Hyperoxia-induced premature senescence requires p53 and pRb, but not mitochondrial matrix ROS. FASEB J. 23, 783–794 (2009)

Ozsolak, F. et al. Direct RNA sequencing. Nature 461, 814–818 (2009)

Hezel, A. F. & Bardeesy, N. LKB1; linking cell structure and tumor suppression. Oncogene 27, 6908–6919 (2008)

Nakada, D., Saunders, T. L. & Morrison, S. J. Lkb1 regulates cell cycle and energy metabolism in haematopoietic stem cells. Nature 10.1038/nature09571 (this issue)

Gan, B. et al. Lkb1 regulates quiescence and metabolic homeostasis of haematopoietic stem cells. Nature 10.1038/nature09595 (this issue)

Watson, M. et al. The small molecule GMX1778 is a potent inhibitor of NAD+ biosynthesis: strategy for enhanced therapy in nicotinic acid phosphoribosyltransferase 1-deficient tumors. Mol. Cell. Biol. 29, 5872–5888 (2009)

Ventura, A. et al. Restoration of p53 function leads to tumour regression in vivo . Nature 445, 661–665 (2007)

Ferrick, D. A., Neilson, A. & Beeson, C. Advances in measuring cellular bioenergetics using extracellular flux. Drug Discov. Today 13, 268–274 (2008)

Robinson, M. D. & Oshlack, A. A scaling normalization method for differential expression analysis of RNA-seq data. Genome Biol. 11, R25 (2010)