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Profilin 1 is essential for retention and metabolism of mouse hematopoietic stem cells in bone marrow

MPG-Autoren
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Böttcher,  Ralph T.
Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society;

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Zitation

Zheng, J., Lu, Z., Kocabas, F., Böttcher, R. T., Costell, M., Kang, X., et al. (2014). Profilin 1 is essential for retention and metabolism of mouse hematopoietic stem cells in bone marrow. BLOOD, 123(7), 992-1001. doi:10.1182/blood-2013-04-498469.


Zitierlink: http://hdl.handle.net/11858/00-001M-0000-0019-D0C7-3
Zusammenfassung
How stem cells interact with the microenvironment to regulate their cell fates and metabolismis largely unknown. Here we demonstrated that the deletion of the cytoskeleton modulating protein profilin 1 (pfn1) in hematopoietic stem cell (HSCs) led to bone marrow failure, loss of quiescence, and mobilization and apoptosis of HSCs in vivo. A switch from glycolysis to mitochondrial respiration with increased reactive oxygen species (ROS) level was also observed in HSCs on pfn1 deletion. Importantly, treatment of pfn1-deficient mice with the antioxidant N-acetyl-L-cysteine reversed the ROS level and loss of quiescence of HSCs, suggesting that the metabolism is mechanistically linked to the cell cycle quiescence of stem cells. The actin-binding and proline-binding activities of pfn1 are required for its function in HSCs. Our study provided evidence that pfn1 at least partially acts through the axis of pfn1/G alpha 13/EGR1 to regulate stem cell retention and metabolism in the bone marrow.