2016 Fiscal Year Final Research Report
The role of Foxf1a for the function of hematopoietic stem cells
| Project/Area Number |
26461452
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Hematology
|
|---|
| Research Institution | Jichi Medical University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2014-04-01 – 2017-03-31
|
| Keywords | 造血幹細胞 / Niche / 細胞周期 / 転写因子 |
|---|
| Outline of Final Research Achievements |
We previously reported that Vinculin is indispensable for the maintenance of hematopoietic stem cells (HSCs). Microarray analysis revealed that the expression of Foxf1a significantly reduced by the inhibition of vinculin. To examine the role of Foxf1a for HSC function, we developed conditional gene-deficient mice. In bone marrow, HSC and megakaryocytes expressed FoxF1a. While white blood cells, red blood cells, and platelets in peripheral blood were not affected, the number of bone marrow cells increased by the deletion of Foxf1a. Competitive repopulation assay of HSC showed that the deletion of Foxf1 deteriorated repopulation capacity of HSCs to reconstitute hematopoiesis. The frequency of long-term culture initiating cells also reduced. Finally, cell cycle analysis by the incorporation of BrdU in vivo revealed the increase in S phase of HSCs by the loss of Foxf1a. These data suggest that Foxf1a regulates quiescent of HSC in bone marrow niche to maintain the hematopoiesis.
|
| Free Research Field |
血液内科学
|
