title: Profilin 1 is essential for retention and metabolism of mouse hematopoietic stem cells in bone marrow.
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.
authors.affiliation: Department of Pathophysiology, Shanghai Universities E-Institute for Chemical Biology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China;
authors.forename: Junke
authors.initials: J
authors.lastname: Zheng
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Lu
authors.forename: Fatih
authors.initials: F
authors.lastname: Kocabas
authors.forename: Ralph T
authors.initials: RT
authors.lastname: Böttcher
authors.forename: Mercedes
authors.initials: M
authors.lastname: Costell
authors.forename: Xunlei
authors.initials: X
authors.lastname: Kang
authors.forename: Xiaoye
authors.initials: X
authors.lastname: Liu
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: Deberardinis
authors.forename: Qianming
authors.initials: Q
authors.lastname: Wang
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Chen
authors.forename: Hesham
authors.initials: H
authors.lastname: Sadek
authors.forename: Cheng Cheng
authors.initials: CC
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000502:physiology; D002465:Cell Movement / Q000235:genetics*; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D006019:Glycolysis / Q000235:genetics*; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D051304:Profilins / Q000502:physiology*; D055153:Stem Cell Niche / Q000235:genetics
chemical_list: C495739:Pfn1 protein, mouse; D051304:Profilins