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, Hesham A Sadek, Chengcheng Zhang

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)992-1001
Number of pages10
Issue number7
StatePublished - Feb 13 2014

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


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