title: 5-hydroxytryptamine synthesized in the aorta-gonad-mesonephros regulates hematopoietic stem and progenitor cell survival.
abstract: The in vitro or ex vivo production of transplantable hematopoietic stem cells (HSCs) holds great promise for the treatment of hematological diseases in the clinic. However, HSCs have not been produced from either embryonic or induced pluripotent stem cells. In this study, we report that 5-hydroxytryptamine (5-HT; also called serotonin) can enhance the generation of hematopoietic stem and progenitor cells (HSPCs) in vitro and is essential for the survival of HSPCs in vivo during embryogenesis. In tryptophan hydroxylase 2-deficient embryos, a decrease in 5-HT synthesized in the aorta-gonad-mesonephros leads to apoptosis of nascent HSPCs. Mechanistically, 5-HT inhibits the AKT-Foxo1 signaling cascade to protect the earliest HSPCs in intraaortic hematopoietic clusters from excessive apoptosis. Collectively, our results reveal an unexpected role of 5-HT in HSPC development and suggest that 5-HT signaling may be a potential therapeutic target for promoting HSPC survival.
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.|University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Junhua
authors.identifier: 0000-0001-7447-0310
authors.initials: J
authors.lastname: Lv
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Lu
authors.identifier: 0000-0003-4788-3237
authors.initials: L
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Ya
authors.identifier: 0000-0001-7093-195X
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Key Laboratory of Arrhythmias, Ministry of Education, East Hospital, Department of Anatomy and Neurobiology, Collaborative Innovation Center for Brain Science, Tongji University School of Medicine, Shanghai 200092, China.
authors.forename: Yu-Qiang
authors.identifier: 0000-0003-1202-4635
authors.initials: YQ
authors.lastname: Ding
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China liuf@ioz.ac.cn.|University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Feng
authors.identifier: 0000-0003-3228-0943
authors.initials: F
authors.lastname: Liu
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism; D017209:Apoptosis; D002470:Cell Survival; D000071161:Forkhead Box Protein O1 / Q000502:physiology; D006066:Gonads / Q000378:metabolism; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008650:Mesonephros / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D012701:Serotonin / Q000502:physiology*; D014365:Tryptophan Hydroxylase / Q000502:physiology
chemical_list: D000071161:Forkhead Box Protein O1; C467200:Foxo1 protein, mouse; D012701:Serotonin; C487802:Tph2 protein, mouse; D014365:Tryptophan Hydroxylase; D051057:Proto-Oncogene Proteins c-akt