Research on spleen microenvironment supporting extramedullary hematopoiesis and its application to the expansion of hematopoietic stem cells

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H05047
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Integrative animal science
• Research Institution: Tokyo University of Science
• Principal Investigator: GOITSUKA RYO 東京理科大学, 研究推進機構生命医科学研究所, 教授 (50301552)
• Co-Investigator(Renkei-kenkyūsha): TAKUBO Keiyo 国立研究開発法人国立国際医療研究センター, 研究所生体恒常性プロジェクト, プロジェクト長 (50502788)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 造血 / 微小環境 / 転写因子 / 発生 / 再生 / 脾臓

Outline of Final Research Achievements

The spleen is a major site for extramedullary hematopoiesis (EMH); however, the niche for EMH in the spleen remain poorly understood compared to the growing understanding of the BM niche at the steady-state as well as in emergency hematopoiesis. In the present study, we demonstrate that mesenchymal progenitor-like cells expressing Tlx1, an essential transcription factor for spleen organogenesis are a major source of HSPC niche factors. Consistently, overexpression of Tlx1 induces EMH, which is associated with mobilization of HSPC into the circulation and their recruitment into the spleen. The alterations in the splenic microenvironment induced by Tlx1 overexpression phenocopy lipopolysaccharide (LPS)-induced EMH, and the conditional loss of Tlx1 abolished LPS-induced splenic EMH. These findings indicate that activation of Tlx1 expression in the postnatal splenic mesenchymal cells is critical for the development of splenic EMH.

Free Research Field

統合動物科学

Academic Significance and Societal Importance of the Research Achievements

緊急時造血の起こる骨髄以外の組織における造血の制御機構が明らかになったことによって、緊急時には骨髄での造血因子の産生は抑制されるのに対して、脾臓では逆に上昇するなど、造血に関わる環境の共通性ならびに特殊性を比較することが可能になった。このことは、基礎医学的には、造血幹・前駆細胞の維持や機能に関わる環境構成要素の共通原理の解明に貢献でき、また、応用医学的には硬組織である骨内腔の骨髄間葉系細胞に比較し、容易に採取可能な脾臓間葉系細胞を用いた造血幹細胞培養系の構築への応用も期待できる。