| First Author | Zheng J | Year | 2014 |
| Journal | Blood | Volume | 123 |
| Issue | 7 | Pages | 992-1001 |
| PubMed ID | 24385538 | Mgi Jnum | J:208691 |
| Mgi Id | MGI:5564835 | Doi | 10.1182/blood-2013-04-498469 |
| Citation | Zheng J, et al. (2014) Profilin 1 is essential for retention and metabolism of mouse hematopoietic stem cells in bone marrow. Blood 123(7):992-1001 |
| abstractText | 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/Galpha13/EGR1 to regulate stem cell retention and metabolism in the bone marrow. |
