Analysis for molecular role of Geminin in hematopoietic and leukemia stem cell

2015 Fiscal Year Final Research Report

• Project/Area Number: 26860734
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Hiroshima University
• Principal Investigator: Ohno Yoshinori 広島大学, 原爆放射線医科学研究所, 助教 (10548986)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: Geminin / 造血幹細胞 / 白血病幹細胞

Outline of Final Research Achievements

Geminin negatively regulates DNA replication and chromatin remodeling through the direct interaction with Cdt1 and Brahma/Brg1, respectively. We previously demonstrated that Polycomb-group complex 1 and Hoxb4/Hoxa9 regulate the activity of hematopoietic stem cells (HSCs) through the ubiquitin proteasome system-mediated direct regulation of Geminin protein, and that Geminin suppresses the E2F-mediated transcriptional activity through the regulation of chromatin remodeling. Geminin is known as a regulator of DNA replication as well as chromatin remodeling. In this study, shRNA-mediated knockdown of Geminin and visualization of Geminin in Geminin-EYFP knockin mice further supported our hypothesis that Geminin acts as a key regulator for determining cell fate of HSCs, i.e., cellular quiescence, self-renewal and differentiation.

Free Research Field

幹細胞機能学