Analysis of hematopoietic stem cell activation induced by Nrf2 inducers

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K18999
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Tohoku University
• Principal Investigator: MURAKAMI Shohei 東北大学, 加齢医学研究所, 産学官連携研究員 (20746911)
• Research Collaborator: SUZUKI Takuma 東北大学, 大学院・医学系研究科・血液・免疫病学分野, 大学院生
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: Keap1-Nrf2制御系 / 造血幹細胞 / 増殖・分化

Outline of Final Research Achievements

To examine whether a stress-responsive transcription factor, Nrf2, contributes to proliferation of hematopoietic stem cells (HSCs) by its transient activation, we treated mice with an Nrf2 inducer, CDDO-Im, and investigated the effects of transient Nrf2 activation on HSCs. Nrf2 activation induced by CDDO-Im treatment promoted HSC proliferation, but bone marrow transplantation experiment revealed that the proliferative HSCs due to the Nrf2 activation easily undergo differentiation and hardly maintain their stem activity. It turned out that under the culture condition with thrombopoietin (TPO), Nrf2 activation enhanced HSC differentiation into megakaryocyte-like cells. Therefore, Nrf2 activation likely induces proliferation/differentiation of HSCs through enhancing the sensitivity to TPO signaling.

Free Research Field

医化学