Cited by 524Hematopoietic Stem Cell TransplantationMetabolism, Diabetes, and CancerBiochemical and Molecular Research

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Lkb1 regulates cell cycle and energy metabolism in haematopoietic stem cells

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Nakada, Daisuke, Saunders, Thomas L., Morrison, Sean J.·2010·Nature

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Abstract

Little is known about metabolic regulation in stem cells and how this modulates tissue regeneration or tumour suppression. We studied the Lkb1 tumour suppressor and its substrate AMP-activated protein kinase (AMPK), kinases that coordinate metabolism with cell growth. Deletion of the Lkb1 (also called Stk11) gene in mice caused increased haematopoietic stem cell (HSC) division, rapid HSC depletion and pancytopenia. HSCs depended more acutely on Lkb1 for cell-cycle regulation and survival than many other haematopoietic cells. HSC depletion did not depend on mTOR activation or oxidative stress. Lkb1-deficient HSCs, but not myeloid progenitors, had reduced mitochondrial membrane potential and ATP levels. HSCs deficient for two catalytic α-subunits of AMPK (AMPK-deficient HSCs) showed similar changes in mitochondrial function but remained able to reconstitute irradiated mice. Lkb1-deficient HSCs, but not AMPK-deficient HSCs, exhibited defects in centrosomes and mitotic spindles in culture, and became aneuploid. Lkb1 is therefore required for HSC maintenance through AMPK-dependent and AMPK-independent mechanisms, revealing differences in metabolic and cell-cycle regulation between HSCs and some other haematopoietic progenitors.

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Viale, A., Pettazzoni, P., Lyssiotis, C. A., Ying, H., Sánchez, N., Marchesini, M., Carugo, A., Green, T., Seth, S., Giuliani, V., et al. (2014) · Nature · doi:10.1038/nature13611 · Cited by 1,259
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Ito, K., Carracedo, A., Weiss, D., Arai, F., Ala, U., Avigan, D., Schafer, Z. T., Evans, R. M., Suda, T., Lee, C., et al. (2012) · Nature Medicine · doi:10.1038/nm.2882 · Cited by 768
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MacIver, N. J., Blagih, J., Saucillo, D. C., Tonelli, L., Griss, T., Rathmell, J. C., & Jones, R. G. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100367 · Cited by 235
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Valcourt, J. R., Lemons, J. M. S., Haley, E. M., Kojima, M. L., Demuren, O. O., & Coller, H. A. (2012) · Cell Cycle · doi:10.4161/cc.19879 · Cited by 240
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Filippi, M., & Ghaffari, S. (2019) · Blood · doi:10.1182/blood-2018-10-808873 · Cited by 209
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Rossi, L., Lin, K. K., Boles, N. C., Yang, L., King, K. Y., Jeong, M., Mayle, A., & Goodell, M. A. (2012) · Cell stem cell · doi:10.1016/j.stem.2012.08.006 · Cited by 205
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Han, X., Li, F., Fang, Z., Gao, Y., Li, F., Fang, R., Yao, S., Sun, Y., Li, L., Zhang, W., et al. (2014) · Nature Communications · doi:10.1038/ncomms4261 · Cited by 194
Temporal Changes in PTEN and mTORC2 Regulation of Hematopoietic Stem Cell Self-Renewal and Leukemia Suppression
Magee, J. A., Ikenoue, T., Nakada, D., Lee, J., Guan, K., & Morrison, S. J. (2012) · Cell stem cell · doi:10.1016/j.stem.2012.05.026 · Cited by 188
Self-citation
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Rafalski, V. A., Mancini, E., & Brunet, A. (2012) · Journal of Cell Science · doi:10.1242/jcs.114827 · Cited by 181
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Rimmelé, P., Liang, R. H.-S., Bigarella, C. L., Kocabaş, F., Xie, J., Serasinghe, M. N., Chipuk, J. E., Sadek, H. A., Zhang, C. C., & Ghaffari, S. (2015) · EMBO Reports · doi:10.15252/embr.201439704 · Cited by 146
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Mapping the in vivo fitness landscape of lung adenocarcinoma tumor suppression in mice
Rogers, Z. N., McFarland, C. D., Winters, I. P., Seoane, J. A., Brady Jennifer, J., Yoon, S. M., Curtis, C. N., Petrov, D. A., & Winslow, M. M. (2018) · Nature Genetics · doi:10.1038/s41588-018-0083-2 · Cited by 125
Metabolism and the Control of Cell Fate Decisions and Stem Cell Renewal
Ito, K., & Ito, K. (2016) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-111315-125134 · Cited by 143
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Helman, A., Cangelosi, A. L., Davis, J. C., Pham, Q., Rothman, A., Faust, A. L., Straubhaar, J., Sabatini, D. M., & Melton, D. A. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.04.004 · Cited by 133
Surviving change: the metabolic journey of hematopoietic stem cells
Kohli, L., & Passegue, E. A. (2014) · Trends in Cell Biology · doi:10.1016/j.tcb.2014.04.001 · Cited by 136
Proteostatic and Metabolic Control of Stemness
García‐Prat, L., Sousa‐Victor, P., & Muñoz‐Cánoves, P. (2017) · Cell stem cell · doi:10.1016/j.stem.2017.04.011 · Cited by 125
Sphingolipid Modulation Activates Proteostasis Programs to Govern Human Hematopoietic Stem Cell Self-Renewal
Xie, S. Z.-J., García‐Prat, L., Voisin, V., Ferrari, R., Gan, O. I., Wagenblast, E., Kaufmann, K. B., Zeng, A. G. X., Takayanagi, S., Patel, I., et al. (2019) · Cell stem cell · doi:10.1016/j.stem.2019.09.008 · Cited by 120
Metabolic Maturation during Muscle Stem Cell Differentiation Is Achieved by miR-1/133a-Mediated Inhibition of the Dlk1-Dio3 Mega Gene Cluster
Wüst, S., Dröse, S., Heidler, J., Wittig, I., Klockner, I., Frankó, A., Bonke, E., Günther, S., Gärtner, U., Boettger, T., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.02.022 · Cited by 122
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Vázquez‐Martín, A., Cufí, S., Corominas-Faja, B., Oliveras‐Ferraros, C., Vellón, L., & Menéndez, J. A. (2012) · Aging · doi:10.18632/aging.100465 · Cited by 116
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Kim, J. K., Jung, Y., Wang, J., Joseph, J., Mishra, A., Hill, E. E., Krebsbach, P. H., Pienta, K. J., Shiozawa, Y., & Taichman, R. S. (2013) · Neoplasia · doi:10.1593/neo.13402 · Cited by 113
Oxidative stress and hypoxia in normal and leukemic stem cells
Testa, U., Labbaye, C., Castelli, G., & Pelosi, E. (2016) · Experimental Hematology · doi:10.1016/j.exphem.2016.04.012 · Cited by 118
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Murray, C. W., Brady, J. J., Tsai, M. K., Li, C., Winters, I. P., Tang, R., Andrejka, L., Ma, R. K., Kunder, C. A., Chu, P., et al. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-1237 · Cited by 111
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Colla, S., Ong, D. S. T., Ogoti, Y., Marchesini, M., Mistry, N. A., Clise-Dwyer, K., Ang, S. A., Storti, P., Viale, A., Giuliani, N., et al. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.04.007 · Cited by 105
Lkb1 controls brown adipose tissue growth and thermogenesis by regulating the intracellular localization of CRTC3
Shan, T., Xiong, Y., Zhang, P., Li, Z., Jiang, Q., Bi, P., Yue, F., Yang, G., Wang, Y., Liu, X., et al. (2016) · Nature Communications · doi:10.1038/ncomms12205 · Cited by 109
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Liang, R., & Ghaffari, S. (2014) · Antioxidants & Redox Signaling · doi:10.1089/ars.2013.5300 · Cited by 106
Targeting LKB1 signaling in cancer
Korsse, S. E., Peppelenbosch, M. P., & van Veelen, W. (2012) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2012.12.006 · Cited by 107
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Timilshina, M., You, Z., Lacher, S. M., Acharya, S., Jiang, L., Kang, Y., Kim, J., Chang, H. W., Kim, K., Park, B., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.05.020 · Cited by 107

Authors: Nakada, D., Saunders, T. L., & Morrison, S. J.
Affiliations: Howard Hughes Medical Institute (US)
University of Michigan (US)
Corresponding author: Morrison, Sean J.
ORCID: Nakada, Daisuke
Saunders, Thomas L.
Morrison, Sean J.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2010-12
Volume: 468
Issue: 7324
Pages: 653-658
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature09571
PMC: PMC3059717
OpenAlex: W2049279804
Cited by: 524
References: 47
Citations by year: 2026: 12 · 2025: 12 · 2024: 29 · 2023: 29 · 2022: 35 · 2021: 27 · 2020: 29 · 2019: 36 · 2018: 41 · 2017: 33 · 2016: 41 · 2015: 33 · 2014: 49 · 2013: 45 · 2012: 39
FWCI: 23.48
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Funders: Howard Hughes Medical Institute
National Cancer Institute (CA46592, P30CA046592)
Topics: Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
Keywords: LKB1, STK11, hematopoietic stem cells, AMPK, energy metabolism, cell cycle regulation, HSC quiescence, HSC depletion, pancytopenia, mitochondrial function, ATP levels, mitotic spindle, aneuploidy, tumor suppression, tissue regeneration, oxidative stress
MeSH terms: Mechanistic Target of Rapamycin Complex 1, Aneuploidy, Animals, Cell Cycle, Cell Division, Cell Survival, Energy Metabolism, Enzyme Activation, Female, Hematopoietic Stem Cells, Male, Mice, Inbred C57BL, Mitochondria, Spindle Apparatus, Pancytopenia, Proteins, Regeneration, Signal Transduction, Cell Death, Protein Serine-Threonine Kinases, Gene Deletion, Centrosome, Sirolimus, Catalytic Domain, Multiprotein Complexes, Mice, AMP-Activated Protein Kinases, TOR Serine-Threonine Kinases

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Lkb1 regulates cell cycle and energy metabolism in haematopoietic stem cells

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