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

Junke Zheng; Zhigang Lu; Fatih Kocabas; Ralph T. Böttcher; Mercedes Costell; Xunlei Kang; Xiaoye Liu; Ralph J. DeBerardinis; Qianming Wang; Guo-Qiang Chen; et al.

(Profiled Authors: Ralph J DeBerardinis; Hesham A Sadek; Chengcheng Zhang)

Blood. 2014;123(7):992-1001.

Abstract

How stem cells interact with the microenvironment to regulate their cell fates and metabolism is 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/Gα13/EGR1 to regulate stem cell retention and metabolism in the bone marrow. © 2014 by The American Society of Hematology.


PMID: 24385538    

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