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Stem cells

LKB1 maintains the balance

Nature Reviews Molecular Cell Biology volume 12, page 5 (2011)Cite this article

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LKB1 regulates the metabolism of many adult cell types, so the authors of the three studies sought to determine whether it also affects metabolic control of HSCs. Using mice in which LKB1 was conditionally deleted from haematopoietic tissues, they observed that loss of LKB1 eventually led to a decline in bone marrow cellularity, progressive pancytopenia (loss of all types of blood cells) and animal death. Moreover, HSCs transiently increased in number, an effect associated with enhanced proliferation, and then markedly decreased. This suggests that LKB1 is necessary to maintain quiescence specifically in HSCs. A requirement for LKB1 in haematopoiesis was revealed in vitro and in vivo: LKB1-deficient HSCs formed fewer colonies than controls in culture; and LKB1-deficient bone marrow showed a markedly decreased ability to repopulate the haematopoietic system of irradiated mice.

The decrease in HSC numbers could be caused by cell death; indeed, all three groups observed increased levels of apoptosis in LKB1-deficient HSCs. Furthermore, Gurumurthy et al. observed increased autophagy in haematopoietic tissues of LKB1-deficient mice, as well as an enhanced expression of phosphorylated histone H2AX, a marker of DNA damage. These findings, together with the observation by Nakada et al. that many LKB1-deficient HSCs are aneuploid, suggest that increased apoptosis could be caused by metabolic or genotoxic stress.

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ORIGINAL RESEARCH PAPERS

  1. Nakada, D., Saunders, T. L. & Morrison, S. J. Lkb1 regulates cell cycle and energy metabolism in haematopoietic stem cells. Nature 468, 653–658 (2010)

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  2. Gurumurthy, S. et al. The Lkb1 metabolic sensor maintains haematopoietic stem cell survival. Nature 468, 659–663 (2010)

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  3. Gan, B. et al. Lkb1 regulates quiescence and metabolic homeostasis of haematopoietic stem cells. Nature 468, 701–704 (2010)

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Authors
  1. Rachel David
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David, R. LKB1 maintains the balance. Nat Rev Mol Cell Biol 12, 5 (2011). https://doi.org/10.1038/nrm3032

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