Variable SATB1 levels regulate hematopoietic stem cell heterogeneity with distinct lineage fate

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461445
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Osaka University
• Principal Investigator: DOI Yukiko 大阪大学, 医学部附属病院, 医員 (60722288)
• Co-Investigator(Renkei-kenkyūsha): TAKEDA Junji 大阪大学, 大学院医学系研究科, 教授 (50163407)
• Research Collaborator: Kohwi-Shigematsu Terumi University of California San Francisco, Department of Orofacial Sciences
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 造血幹細胞 / リンパ球初期分化 / SATB1

Outline of Final Research Achievements

Hematopoietic stem cells (HSCs) comprise a heterogeneous population. However, the mechanisms involved in maintaining this heterogeneity remain unclear. Here, we show that SATB1, a genome organizer, is involved in regulating the heterogeneity of HSCs. In conditional SATB1-knockout mice, SATB1 was indispensable for self-renewal and lymphopoiesis of adult HSCs. HSCs from SATB1/Tomato-knock-in reporter mice were classified based on SATB1/Tomato intensity. Transplantation, transcriptional and cell culture studies revealed stronger differentiation towards the lymphocytic lineage with high SATB1 levels, whereas SATB1- HSCs followed the myeloid lineage. Importantly, the SATB1- and SATB1+ HSC population were interconvertible upon transplantation. These results suggest that SATB1 levels regulate the maintenance of HSC multipotency, variations in which contribute to HSC heterogeneity.

Free Research Field

血液内科学