Age-related alterations of hematopoietic stem and progenitor cells due to failure of Bach transcription factors

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H04021
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Medium-sized Section 48:Biomedical structure and function and related fields
• Research Institution: Tohoku University
• Principal Investigator: IGARASHI Kazuhiko 東北大学, 医学系研究科, 教授 (00250738)
• Co-Investigator(Kenkyū-buntansha): 張替 秀郎 東北大学, 医学系研究科, 教授 (50302146)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 造血幹細胞 / 老化 / 転写因子 / 遺伝子発現 / 骨髄異形成症候群

Outline of Final Research Achievements

We aimed to understand the functions of BACH1 and BACH2 in the regulation of hematopoietic cell differentiation. By generating and analyzing mice lacking both of these genes, we found that these mice showed reduced differentiation of red blood cells and lymphoid cells, which were similar to alterations observed in myelodysplastic syndrome (MDS). By analyzing gene expression of the bone marrow cells of patients of MDS, we found that the expression of BACH2 was reduced along the progression of the disease, suggesting that a reduction in the function of BACH2 is involved in the disease progress including anemia and immunodeficiency. BACH1 and BACH2 were found to promote differentiation of erythroid cells and lymphoid cells by repressing the expression of genes important for the differentiation and/or function of myeloid cells.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

加齢に伴い、造血幹細胞の機能が低下し、貧血や免疫不全が生じることが判明しつつある。しかし、この加齢変化の原因は不明である。本研究で作成し検討したBACH1/BACH2二重欠損マウスの血液像は、ヒトで観察される造血系の加齢変化と合致する所見であった。今後、加齢とともに造血系細胞でBACH1やBACH2の発現が低下するのか、それら転写因子の標的遺伝子である骨髄球系遺伝子の発現は亢進するのか、などを調べることで、ヒト造血系老化の分子機構に迫ることができると考えられた。