论文
论文题目: 5-Hydroxytryptamine Synthesized in the Aorta-Gonad-Mesonephros Regulates Hematopoietic Stem and Progenitor Cell Survival
论文题目英文:
作者: 吕军华①,王璐①,高雅,#丁玉强,刘峰*
论文出处:
年: 2017
卷: 214
期: 2
页: 529-545
联系作者: 刘峰
发表期刊: Journal of Experimental Medicine
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论文连接 http://jem.rupress.org/content/214/2/529
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摘要: 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.
英文摘要:
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