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5-hydroxytryptamine synthesized in the aorta-gonad-mesonephros regulates hematopoietic stem and progenitor cell survival
- Source :
- The Journal of Experimental Medicine
- Publication Year :
- 2017
- Publisher :
- The Rockefeller University Press, 2017.
-
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.<br />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.
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 15409538 and 00221007
- Volume :
- 214
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- The Journal of Experimental Medicine
- Accession number :
- edsair.doi.dedup.....f537fa2e5e713c6ac67bc4158822b3f1