the cytosolic protein g0s2 maintains quiescence in hematopoietic stem cells胞质蛋白g0s2保持静止在造血干细胞.pdf

The Cytosolic Protein G0S2 Maintains Quiescence in Hematopoietic Stem Cells 1 1 1 2 1,3 Takeshi Yamada , Chun Shik Park , Audrea Burns , Daisuke Nakada , H. Daniel Lacorazza * 1 Department of Pathology Immunology, Baylor College of Medicine, Texas Children’s Hospital, Houston, Texas, United States of America, 2 Department of Molecular and Human Genetics, Baylor College of Medicine, Texas Children’s Hospital, Houston, Texas, United States of America, 3 Department of Pediatrics, Baylor College of Medicine, Texas Children’s Hospital, Houston, Texas, United States of America Abstract Bone marrow hematopoietic stem cells (HSCs) balance proliferation and differentiation by integrating complex transcriptional and post-translational mechanisms regulated by cell intrinsic and extrinsic factors. We found that transcripts of G0/G1 switch gene 2 (G0S2) are enriched in lineage2 Sca-1+ c-kit+ (LSK) CD150+ CD482 CD412 cells, a population highly enriched for quiescent HSCs, whereas G0S2 expression is suppressed in dividing LSK CD150+ CD482 cells. Gain-of-function analyses using retroviral expression vectors in bone marrow cells showed that G0S2 localizes to the mitochondria, endoplasmic reticulum, and early endosomes in hematopoietic cells. Co-transplantation of bone marrow cells transduced with the control or G0S2 retrovirus led to increased chimerism of G0S2-overexpressing cells in femurs, although their contribution to the blood was reduced. This finding was correlated with increased quiescence in G0S2-overexpressing HSCs (LSK CD150+ CD482) and progenitor cells (LS2K). Conversely, silencing of