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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Méndez‐Ferrer, S. (2023) · eLife · doi:10.7554/elife.87674.1.sa2
Reviewer #1 (Public Review): Context-Dependent Modification of PFKFB3 in Hematopoietic Stem Cells Promotes Anaerobic Glycolysis and Ensures Stress Hematopoiesis
(2023) · eLife · doi:10.7554/elife.87674.1.sa1
Reviewer #2 (Public Review): Context-Dependent Modification of PFKFB3 in Hematopoietic Stem Cells Promotes Anaerobic Glycolysis and Ensures Stress Hematopoiesis
(2023) · eLife · doi:10.7554/elife.87674.1.sa0
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Stem Cells and Leukemia
Giambra, V., & Jenkins, C. R. (2011) · Springer eBooks · doi:10.1007/978-94-007-2801-1_13

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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