title: Rheb1-mTORC1 maintains macrophage differentiation and phagocytosis in mice.
abstract: Ras homolog enriched in brain (Rheb1) is a small GTPase and is known to be a direct activator of mTORC1. Dysregulation of Rheb1 has been shown to impair the cellular-energetic state and cell homeostasis. However, the role of Rheb1 in monocytes/macrophages differentiation and maturation is not clear. Here, we investigate the role of Rheb1 in mouse myelopoiesis using a Rheb1 conditional deletion murine model. We found that the absolute number of macrophages decreased in the bone marrow (BM) of Rheb1-deficient mice. Loss of Rheb1 inhibited the monocyte-to-macrophage differentiation process. Additionally, Rheb1 deletion reduced phagocytosis ability of macrophages by inhibiting the mTORC1 signaling pathway. Furthermore, 3BDO (an activator of mTORC1) rescued the phagocytosis ability of Rheb1-deficient macrophages. Thus, Rheb1 is critical for macrophage production and phagocytosis and executes these activities possibly via mTORC1-dependent pathway.
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.
authors.forename: Minghao
authors.initials: M
authors.lastname: Li
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.
authors.forename: Wanzhu
authors.initials: W
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.
authors.forename: Haoyue
authors.initials: H
authors.lastname: Liang
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ji
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.
authors.forename: Yanxin
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.
authors.forename: Hanzhi
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Pathology and Laboratory Medicine, School of Medicine, Temple University, Philadelphia, PA 19140, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Cheng
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Yuan
mesh_terms: D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D015973:Gene Expression Regulation, Leukemic; D063990:Gene Ontology; D006410:Hematopoiesis; D008099:Liver / Q000196:embryology; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism*; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D008822:Mice, Transgenic; D020559:Monomeric GTP-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000378:metabolism*; D009479:Neuropeptides / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010587:Phagocytosis; D000076205:Ras Homolog Enriched in Brain Protein; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D046912:Multiprotein Complexes; D009479:Neuropeptides; D000076205:Ras Homolog Enriched in Brain Protein; C490213:Rheb protein, mouse; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D020559:Monomeric GTP-Binding Proteins
keywords: 3BDO; Macrophage; Phagocytosis; Rheb1; S6; mTOR