The role of SATB1-MS4A3 in the differentiation of hematopoietic stem cells

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461412
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Kobe Shoin Women's University
• Principal Investigator: SATOH YUSUKE 神戸松蔭女子学院大学, 人間科学部, 准教授 (20506307)
• Co-Investigator(Renkei-kenkyūsha): TANAKA HIROKAZU 近畿大学, 医学部, 講師 (40360846)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 造血幹細胞 / SATB1 / MS4A3

Outline of Final Research Achievements

We generated hematological-lineage restricted SATB1 conditional knock out (cKO) mice. Analyzing the adult bone marrow (BM) in these mice, we observed a significant decrease in the number of HSCs as compared to those in their wild type (WT) littermates. SATB1 cKO mice-derived HSCs showed lower BM reconstitution ability than WT HSCs. Next, we generated SATB1 reporter mice, and examined the early differentiation of HSCs. We found that the HSC fraction of adult BM consists of SATB1－ and SATB1+ cells. In transplantation experiments, the SATB1+ HSCs produced more lymphocytic cells and fewer myeloid cells in the recipients.
The membrane protein MS4A3 is negatively regulated by SATB1, and we found that MS4A3 expression was observed in primary acute myeloid leukemia cases. In addition , a MS4A3 antibody induced complement-dependent cell death in several human AML lines. These results suggest that MS4A3 may serve as a putative therapeutic target to treat myeloid malignancies.

Free Research Field

血液内科学