Role of transcriptional co-repressor, TIF1b, in hematopoietic stem cell
| Project/Area Number |
21790906
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Hematology
|
|---|
| Research Institution | Chiba University |
|---|
Principal Investigator |
MIYAGI Satoru Chiba University, 大学院・医学研究院, 助教 (20400997)
|
|---|
| Project Period (FY) |
2009 – 2010
|
| Project Status |
Completed (Fiscal Year 2010)
|
| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
|---|
| Keywords | 造血幹細胞 / 自己複製 / 細胞分化 / クロマチン / 転写制御 / 核構造 / 遺伝子発現制御 |
|---|
| Research Abstract |
To assess the role of Tifb in the hematopoietic stem cells (HSCs), we disrupted the Tif1b gene specifically in hematopoietic cells. Tif1b^<F/F>-Tie2-Cre embryos died at mid-gestation due to anemia. In the mutant embryo, erythroblast maturation beyond the proerythroblast and survival of erythroblast were severely abrogated, indicating that Tif1b plays a critical role in embryonic erythropoiesis. Then, to elucidate the Tif1b function in HSC, we performed a series of transplantation assays and showed the cell-autonomous requirement for Tif1b in HSC repopulating capacity. Moreover, Tif1b^<F/F>-Tie2-Cre KSL cells proliferated and differentiated into myeloid cells poorly in vitro. To address the mechanism underlying the proliferation defect of Tif1b-deficient KSL cells, we conducted the microarray analysis and found that p21, but not p16, p19 and p57, was up-regulated in Kif1b-deficient KSL cells. Together, our findings suggest repression of p21 expression mediated by Tif1b is a critical for the maintenance of HSCs. On the other hand, we also observed that reduction and inappropriate localization of HP1a protein in the Kif1b-deficient KSL cells, so, TIF1b and HP1a may collaborate to repress the p21 expression.
|
Report
(3 results)
Research Products
(23 results)
-
[Journal Article] Direct activation of STAT5 by ETV6-LYN fusion protein promotes induction of myeloproliferative neoplasm with myelofibrosis.2011
Author(s)
Takeda, Y., Nakaseko, C., Tanaka, H., Takeuchi, M., Yui, M., Saraya, A., Miyagi, S., Wang, C., Tanaka, S., Ohwada, C., Sakaida, E., Yamaguchi, N., Yokote, K., Hennighausen, L., Iwama A.
-
Journal Title
Br.J.Haematol. 153
Pages: 589-598
Related Report
Peer Reviewed
-
-
-
[Journal Article] The polycomb group gene product Ezh2 regulates proliferation and differentiation of murine hepatic stem/progenitor cells.2010
Author(s)
Aoki, R., Chiba, T., Miyagi, S., Negishi, M., Konuma, T., Taniguchi, H., Ogawa, M., Yokosuka, O., Iwama, A.
-
Journal Title
J Hepatol. 52
Pages: 854-863
Related Report
Peer Reviewed
-
[Journal Article] The polycomb-group gene Bmil promotes hepatic stem cell expansion and tumorigenicity in both Ink4a/Arf-dependent and independent manners.2010
Author(s)
Chiba T, Seki A, Aoki R, Ichikawa H, Negishi M, Miyagi S, Oguro H, Saraya A, Kamiya A, Nakauchi H, Yokosuka O, Iwama A.
-
Journal Title
Hepatology. 52
Pages: 1111-1123
Related Report
Peer Reviewed
-
[Journal Article] Identification of a novel TEL-Lyn fusion gene in primary myelofibrosis.2010
Author(s)
Tanaka, H., Takeuchi, M., Takeda, Y., Sakai, S., Abe, D., Ohwada, C., Sakaida, E., Shimizu, N., Saito, Y., Miyagi, S., Iwama, A., Nakaseko, C.
-
Journal Title
Leukemia 24
Pages: 197-200
Related Report
Peer Reviewed
-
-
-
-
-
-
[Journal Article] Distinct expression of polycomb group proteins EZH2 and BMI1 in hepatocellular carcinoma.2009
Author(s)
Yonemitsu, Y., Imazeki, F., Chiba, T., Fukai, K., Nagai, Y., Miyagi, S., Arai, M., Aoki, R., Miyazaki, M., Nakatani, Y., Iwama, A., Yokosuka, O.
-
Journal Title
Hum.Pathol. 40
Pages: 1304-1311
Related Report
Peer Reviewed
-
-
-
-
[Journal Article] Forced expression of the histone demethylase Fbxl10 maintains self-renewing hematopoietic stem cells.
Author(s)
Konuma, T., Nakamura, S., Miyagi, S., Negishi, M., Chiba, T., Oguro, H., Yuan, J., Mochizuki-Kashio, M., Ichikawa, H., Miyoshi, H., Vidal, M., Iwama, A.
-
Journal Title
Related Report
Peer Reviewed
-
-
-
-
-
-
-
