Elucidation of the formation and the maintenance of hematopoietic cell clusters, which contain hematopoietic stem cells, along with endothelial cells of the dorsal aorta in midgestation mouse embryos

2016 Fiscal Year Final Research Report

• Project/Area Number: 26440118
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Developmental biology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Nobuhisa Ikuo 東京医科歯科大学, 難治疾患研究所, 准教授 (40332879)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: AGM / Hematopoiesis / Sox17 / Notch1 / VE-Cad

Outline of Final Research Achievements

During mouse development, hematopoietic stem cells (HSCs) firstly arise intra-aortic cell clusters (IAHCs) of the dorsal aorta at embryonic day 10.5. Introduction of transcription factor Sox17 into cells of IAHCs leads to consistent formation of cell clusters containing HSCs in vitro. We examined the molecular mechanism of this phenomenon in this project. We showed the importance of the thrombopoietin/c-Mpl signal pathway in Sox17-transduced hematopoietic cell clusters. Moreover, we demonstrated that the binding of Sox17 to the Notch1 promoter induced the Notch1-expression and Notch1 intra-cellular domain (NICD, the active form)-transduced cells maintained the undifferentiated state. Cells transduced with Hes1, which is one of the target genes of the Notch signaling pathway, have a capacity to maintain the undifferentiated state. Furthermore, the Sox17-induced adherent molecule vascular endothelial cadherin has a role of the formation and the maintenance of hematopoietic cell clusters.

Free Research Field

幹細胞生物学