2015 Fiscal Year Final Research Report
Analysis of an uncharacterized gene essential for hematopoietic development
Project/Area Number |
26860731
|
Research Category |
Grant-in-Aid for Young Scientists (B)
|
Allocation Type | Multi-year Fund |
Research Field |
Hematology
|
Research Institution | Osaka University |
Principal Investigator |
|
Research Collaborator |
TANAKA Sachiyo 大阪大学, 医学系研究科, 特任研究員
|
Project Period (FY) |
2014-04-01 – 2016-03-31
|
Keywords | 造血 / 新規遺伝子 / アポトーシス / コンディショナルノックアウトマウス |
Outline of Final Research Achievements |
Using our previously established homozygous mutant mouse ESC bank, we performed in vitro differentiation screening assays. We identified a previously uncharacterized gene, which we named Ahed, whose null mutant ESCs showed the attenuated production of blood cells during hematopoietic differentiation. This observation was substantiated by hematopoietic cell-specific ablation of Ahed by crossing floxed mice with Vav1-cre transgenic mice, which caused fetal anemia from E14.5 onwards, leading to perinatal lethality. E14.5 fetal liver hematopoietic stem/progenitor cells (LSK cells) from conditional knockout embryos produced less and smaller colonies in a methylcellulose culture. We found that Ahed encodes a nuclear protein whose loss induces upregulation of the genes involved in apoptosis and cell cycle arrest. Furthermore, Ahed-null E14.5 LSK cells revealed marked apoptosis during culture.
|
Free Research Field |
血液内科学
|