Control of differentiation and function of hematopoietic cells by, BCL6 and AP-1 family

2007 Fiscal Year Final Research Report Summary

• Project/Area Number: 18591074
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Kumamoto University
• Principal Investigator: OKADA Seiji Kumamoto University, Center for AIDS Research Division of Hematopoiesis, Professor (50282455)
• Co-Investigator(Kenkyū-buntansha): SUZU Shinya Kumamoto University, Center for AIDS Research Division of Hematopoiesis, Associate Professor (80363513)
• Project Period (FY): 2006 – 2007
• Keywords: BCL6 / AP-1 / c-Fos / Hematopoietic cells / Erythroblast / Dendritic cells / B cells

Research Abstract

The proto-oncogene bcl-6 and c-fos are ubiquitously expressed in various tissues, and play important role for the differentiation, proliferation, apoptosis and oncogeneisis. In this study, I focused on the function of bcl-6 and c-fos for the hematologic cells, using transgenic and gene deficient mice.
1. Function of Bcl-6 on erythroid differentiation
Bcl-6 detected in the TER119highCD7lhigh subset of erythroblasts in the spleen of neonatal mice may be required to retain the erythroblasts in the cell proliferation stage. In addition, we found that ABCG-2 is also expressed in erythroblast of all of the maturation stage.
2. Function of Bcl-6 on dendritic cell differentiation
Bcl-6 deficient mice showed decreased umber of dendritic cells in spleen. Especially CD8+ subfraction of dendriti cells was completely deficient,.
3. Function ofBCL6 on B cell differentiation
We have found that ADAR1 (RNA-editing adenosine deaminase) is one of the target gene of BCL6, and loss of Bc16 cause the higher frequency of somatic hypermultation on B cells.
4. Effect of c-Fos ro the regulation of TCRβ recombination.
We have found that c-fos directly promotes RAG1/2 binding to the RSS and regulate TCRβ recombination ordering and allelic exclusion.
5. Analysis of hematopoietic niche in c-Fos deficient mice.
We have found that Magakaryocyte-like cells are appeared in the spleen of c-Fos deficient mice and play an important role in the hematopoietic niche.

Research Products

• [Journal Article] Interaction between Hck and HIV-1 Nef negatively regulates cell surf ace expression of M-CSF receptor (2008)
  • Author(s): Hiyoshi M
  • Journal Title: Blood 111 Pages: 243-250
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Interaction between Hck and HIV-1 Nef negatively regulates cell surface expression of M-CSF receptor (2008)
  • Author(s): Hiyoshi, M., Suzu, S., Yoshidomi, Y., Hassan, R., Harada, H., Sakashita, N., Akari, H., Motoyoshi, K., Okada, S
  • Journal Title: Blood 111, (1) Pages: 243-250
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Erythroblasts highly express the ABC transporter Bcrp1/ABC G2 but do not show the side population(SP)phenotype (2007)
  • Author(s): Yamamoto K
  • Journal Title: Immunol Lett 114 Pages: 52-58
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Erythroblasts highly express the ABC transporter Bcrp1/ABCG2 but do not show the side population(SP) phenotype (2007)
  • Author(s): Yamamoto, K., Suzu, S., Yoshidomi, Y., Hiyoshi, M., Harada, H., Okada, S
  • Journal Title: Immunol Lett 114, (1) Pages: 52-58
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] 髄外造血機構を用いた造血幹細胞ニッチの解析 (2007)
  • Author(s): 水上 拓郎
  • Organizer: 第69回日本血液学会総会
  • Place of Presentation: 横浜
  • Year and Date: 20071011-13
  • Description: 「研究成果報告書概要(和文)」より
• [Remarks] 「研究成果報告書概要(和文)」より
  • URL: http://www.caids.kumamoto-u.ac.jp/data/yobou/default.html