Roles of BMP signaling in maintenance of cell stemness

2015 Fiscal Year Final Research Report

• Project/Area Number: 24390070
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: The University of Tokyo
• Principal Investigator: MIYAZONO Kohei 東京大学, 医学(系)研究科(研究院), 教授 (90209908)
• Co-Investigator(Renkei-kenkyūsha): KOINUMA Daizo 東京大学, 大学院医学系研究科, 准教授 (80375071)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Keywords: 細胞医化学 / ゲノム医化学 / 細胞内シグナル伝達 / 発生医学

Outline of Final Research Achievements

BMPs are key serum-derived factors that act to sustain self-renewal and pluripotency of mouse ES cells. In contrast, human ES cells share defining features with mouse epiblast stem cells (mEpiSC). BMP-4 induces differentiation of mEpiSCs into extraembryonic lineage or mesendoderm. We found that the BMP-Smad pathway is dispensable for maintaining naive pluripotency, and that the transcriptional factor KLF4 plays a key role in the suppression of Smad1 activity. We also found that the MEK5-ERK5 pathway mediates BMP-4-induced self-renewal of mESCs by inducing KLF2.
We have investigated the roles of BMPs in regulation of glioma-initiating cells (GICs). In the orthotopic transplantation model, BMP signaling repressed the tumorigenic activity through loss of stemness properties of GICs. We further performed DNA microarray and RNA-seq analyses to identify novel target genes of BMP signaling in GICs, and found that PRRX1 plays an important role in regulation of the differentiation of GICs.

Free Research Field

医化学一般