5-hydroxytryptamine synthesized in the aorta-gonad-mesonephros regulates hematopoietic stem and progenitor cell survival.
Junhua LvLu WangYa GaoYu-Qiang DingFeng LiuPublished in: The Journal of experimental medicine (2016)
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.
Keyphrases
- stem cells
- oxidative stress
- endoplasmic reticulum stress
- signaling pathway
- aortic valve
- free survival
- cell death
- cell cycle arrest
- pulmonary artery
- primary care
- single cell
- risk assessment
- genome wide
- machine learning
- pi k akt
- mesenchymal stem cells
- cell therapy
- climate change
- physical activity
- weight loss
- oxide nanoparticles