Hippo Kinase MST1-Mediated Cell Metabolism Reprograms the Homeostasis and Differentiation of Granulocyte Progenitor Cells. 2023

Anna Jia, and Yufei Wang, and Qiuli Yang, and Yuexin Wang, and Yijin Huang, and Yujing Bi, and Guangwei Liu
Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing, China.

The mechanism of the development of granulocyte progenitor cells into neutrophils under steady-state and pathological conditions remains unclear. In this study, our results showed that with the development of neutrophils from hematopoietic stem cells to mature neutrophils, the expression level of the Hippo kinase MST1 gradually increased. Mst1-specific deficiency in myeloid cells caused neutrophilia, with an expanded granulocytic compartment resulting from a cell-autonomous increase in the number of granulocyte-macrophage progenitors under steady-state conditions and during Listeria monocytogenes infection. Mechanistically, mTOR and HIF1α signaling are required for regulating the balance between glycolysis and succinate dehydrogenase-mediated oxidative phosphorylation, which is crucial for Mst1-/--induced proliferation of granulocyte-monocyte progenitors, lineage-decision factor C/EBPα expression, and granulopoiesis. HIF1α directly regulated C/EBPα promoter activities. Blocking mTOR and HIF1α or adjusting the balance between glycolysis and succinate dehydrogenase-mediated oxidative phosphorylation reversed the granulopoiesis induced by Mst1-/- under steady-state conditions or infection in mice. Thus, our findings identify a previously unrecognized interplay between Hippo kinase MST1 signaling and mTOR-HIF1α metabolic reprogramming in granulocyte progenitor cells that underlies granulopoiesis.

UI MeSH Term Description Entries
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D006706 Homeostasis The processes whereby the internal environment of an organism tends to remain balanced and stable. Autoregulation
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013385 Succinate Dehydrogenase A flavoprotein containing oxidoreductase that catalyzes the dehydrogenation of SUCCINATE to fumarate. In most eukaryotic organisms this enzyme is a component of mitochondrial electron transport complex II. Succinic Oxidase,Fumarate Reductase,Succinic Dehydrogenase,Dehydrogenase, Succinate,Dehydrogenase, Succinic,Oxidase, Succinic,Reductase, Fumarate
D042381 Granulocyte Precursor Cells The cells in the granulocytic series that give rise to mature granulocytes (NEUTROPHILS; EOSINOPHILS; and BASOPHILS). These precursor cells include myeloblasts, promyelocytes, myelocytes and metamyelocytes. Myeloblasts,Promyelocytes,Granulocyte Progenitor Cells,Granulocyte Progenitors,Granulocytic Precursor Cells,Metamyelocytes,Myeloblast,Myelocytes,Premyelocytes,Progranulocytes,Cell, Granulocyte Precursor,Cell, Granulocyte Progenitor,Cell, Granulocytic Precursor,Cells, Granulocyte Precursor,Cells, Granulocyte Progenitor,Cells, Granulocytic Precursor,Granulocyte Precursor Cell,Granulocyte Progenitor,Granulocyte Progenitor Cell,Granulocytic Precursor Cell,Metamyelocyte,Myelocyte,Precursor Cell, Granulocyte,Precursor Cell, Granulocytic,Precursor Cells, Granulocyte,Precursor Cells, Granulocytic,Premyelocyte,Progenitor Cell, Granulocyte,Progenitor Cells, Granulocyte,Progenitor, Granulocyte,Progenitors, Granulocyte,Progranulocyte,Promyelocyte
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D058570 TOR Serine-Threonine Kinases A serine threonine kinase that controls a wide range of growth-related cellular processes. The protein is referred to as the target of RAPAMYCIN due to the discovery that SIROLIMUS (commonly known as rapamycin) forms an inhibitory complex with TACROLIMUS BINDING PROTEIN 1A that blocks the action of its enzymatic activity. TOR Kinase,TOR Kinases,TOR Serine-Threonine Kinase,Target of Rapamycin Protein,mTOR Serine-Threonine Kinase,mTOR Serine-Threonine Kinases,FK506 Binding Protein 12-Rapamycin Associated Protein 1,FKBP12-Rapamycin Associated Protein,FKBP12-Rapamycin Complex-Associated Protein,Mammalian Target of Rapamycin,Mechanistic Target of Rapamycin Protein,RAFT-1 Protein,Rapamycin Target Protein,Target of Rapamycin Proteins,mTOR Protein,FK506 Binding Protein 12 Rapamycin Associated Protein 1,FKBP12 Rapamycin Associated Protein,FKBP12 Rapamycin Complex Associated Protein,Kinase, TOR,Kinase, TOR Serine-Threonine,Kinase, mTOR Serine-Threonine,Kinases, TOR Serine-Threonine,Kinases, mTOR Serine-Threonine,Protein Target, Rapamycin,Protein, RAFT-1,Protein, mTOR,RAFT 1 Protein,Rapamycin Protein Target,Serine-Threonine Kinase, TOR,Serine-Threonine Kinase, mTOR,Serine-Threonine Kinases, TOR,Serine-Threonine Kinases, mTOR,TOR Serine Threonine Kinase,TOR Serine Threonine Kinases,mTOR Serine Threonine Kinase,mTOR Serine Threonine Kinases

Related Publications

Anna Jia, and Yufei Wang, and Qiuli Yang, and Yuexin Wang, and Yijin Huang, and Yujing Bi, and Guangwei Liu
March 2023, Immunology,
Anna Jia, and Yufei Wang, and Qiuli Yang, and Yuexin Wang, and Yijin Huang, and Yujing Bi, and Guangwei Liu
January 1983, Haematology and blood transfusion,
Anna Jia, and Yufei Wang, and Qiuli Yang, and Yuexin Wang, and Yijin Huang, and Yujing Bi, and Guangwei Liu
June 2017, Science (New York, N.Y.),
Anna Jia, and Yufei Wang, and Qiuli Yang, and Yuexin Wang, and Yijin Huang, and Yujing Bi, and Guangwei Liu
June 2023, Nature communications,
Anna Jia, and Yufei Wang, and Qiuli Yang, and Yuexin Wang, and Yijin Huang, and Yujing Bi, and Guangwei Liu
March 2020, Stem cell reports,
Anna Jia, and Yufei Wang, and Qiuli Yang, and Yuexin Wang, and Yijin Huang, and Yujing Bi, and Guangwei Liu
August 2012, Proceedings of the National Academy of Sciences of the United States of America,
Anna Jia, and Yufei Wang, and Qiuli Yang, and Yuexin Wang, and Yijin Huang, and Yujing Bi, and Guangwei Liu
January 2019, Journal of immunology (Baltimore, Md. : 1950),
Anna Jia, and Yufei Wang, and Qiuli Yang, and Yuexin Wang, and Yijin Huang, and Yujing Bi, and Guangwei Liu
October 2019, Biochimica et biophysica acta. Molecular cell research,
Anna Jia, and Yufei Wang, and Qiuli Yang, and Yuexin Wang, and Yijin Huang, and Yujing Bi, and Guangwei Liu
October 2023, Nature communications,
Anna Jia, and Yufei Wang, and Qiuli Yang, and Yuexin Wang, and Yijin Huang, and Yujing Bi, and Guangwei Liu
January 2023, Cancers,
Copied contents to your clipboard!