1. 5-hydroxytryptamine synthesized in the aorta-gonad-mesonephros regulates hematopoietic stem and progenitor cell survival
- Author
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Lu Wang, Ya Gao, Feng Liu, Yu-Qiang Ding, and Junhua Lv
- Subjects
0301 basic medicine ,endocrine system ,Serotonin ,Cell Survival ,MAP Kinase Signaling System ,Immunology ,Apoptosis ,Biology ,Tryptophan Hydroxylase ,Article ,03 medical and health sciences ,Mice ,Aorta-gonad-mesonephros ,Immunology and Allergy ,Animals ,Progenitor cell ,Induced pluripotent stem cell ,Gonads ,Research Articles ,Aorta ,Forkhead Box Protein O1 ,food and beverages ,Hematopoietic Stem Cells ,Embryonic stem cell ,Cell biology ,Hematopoiesis ,Mice, Inbred C57BL ,Haematopoiesis ,030104 developmental biology ,Mesonephros ,Signal transduction ,Stem cell ,Proto-Oncogene Proteins c-akt ,Ex vivo - Abstract
Lv et al. show that in mice, 5-HT can be synthesized in the aorta-gonad-mesonephros and acts as a novel endogenous regulator of hematopoietic stem and progenitor cell (HSPC) development. The promoting effect of 5-HT on the survival of HSPCs in the intraaortic hematopoietic cluster is mediated through Htr5a-AKT-Foxo1 signaling., 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.
- Published
- 2017