Department of Advanced Science for Biomolecules
ProjectLeader

Takahiko Hara Stem Cell Project

Blood regeneration from ESC/iPSC anddevelopment of novel anti-cancer drugs

Tanegashima K, Takahashi R, Nuriya
H, Iwase R, Naruse N, Tsuji K,
Shigenaga A, Otaka A, and Hara T.
(2017) “CXCL14 acts as a specificcarrier of CpG DNA into dendritic
cells and activates Toll-like receptor
9-mediated adaptive immunity.”
EBioMed. 24: 247-256.
Tanegashima K, Sato-Miyata Y,Funakoshi M, Nishito Y, Aigaki T, andHara T. (2017) “Epigenetic regulationof the glucose transporter geneSlc2a1 by β-hydroxybutyrate underlies
preferential glucose supply to thebrain of fasted mice.” Genes Cells
22: 71-83.
Suzuki T, Kazuki Y, Oshimura M,and Hara T. (2016) “Highly efficienttransfer of chromosomes to a broad
range of target cells using Chinese
hamster ovary cells expressing murine
leukemia virus-derived envelope
proteins.” PLoS ONE 11: e0157187.
Kodaka Y, Tanaka K, Kitajima,Tanegashima K, Matsuda R, and HaraT.(2015) “LIM homeobox transcription
factor Lhx2 inhibits skeletal muscledifferentiation in part via transcriptional
activation of Msx1 and Msx2.” Exp.
Cell Res. 331: 309-319.
Tanaka K, Kondo K, Kitajima K,Muraoka M, Nozawa A, and Hara T.
(2013) “Tumor-suppressive function ofprotein-tyrosine phosphatase nonreceptor type 23 in testicular germ celltumors is lost upon overexpressionof miR142-3p microRNA.” J. Biol.
Chem. 288: 23990-23999.
Kitajima K, Minehata K, Sakimura
K, Nakano T, and Hara T. (2011)“In vitro generation of HSC-like cells
from murine ESCs/iPSCs by enforced
expression of LIM-homeobox
transcription factor Lhx2.” Blood 117:3748-3758.

Stem Cell
59Dr. Yamanaka’s inducible pluripotent stem cell (iPSC) technology
has opened a new avenue to overcome incurable diseases bytransplantation of missing cells. In 2011, we discovered thatoverexpression of Lhx2 in hemogenic mesodermal cells resulted in exvivo expansion of transplantable hematopoietic stem cells (HSCs) frommouse embryonic stem cells (ESCs) and iPSCs. Since then, we aremaking great efforts to improve the system and apply this method tohuman iPSCs. We believe that comparison of the in vitro differentiation
capacity of hematopoietic cells between mouse and human iPSCs
would uncover novel and fundamental aspects of human HSC
development.

“We are making efforts to derive HSCs from human
iPSCs in vitro. We are also challenging to develop
novel anti-leukemia drugs and chemokine-based
anti-cancer drugs.”
The presence of cancer stem cells has been proposed in various typesof human cancer. As with tissue stem cells, cancer stem cells residein a niche and stay dormant, thereby surviving chemotherapy andradiotherapy. Presumably, both tissue and cancer stem cells commonly
express critical transcriptional regulators and signal transducers. We
have already identified DDX1 and PTPN23 as essential molecules forthe onset of testicular tumors.
In 2007, we discovered that CXCL14, a CXC-type chemokine, is oneof the causative factors for obesity-associated diabetes. In contrast,
CXCL14 is known to possess tumor-suppressive activity against lungand oral carcinomas. Recently, we discovered that CXCL14 binds
to CXCR4 with high affinity, thereby inhibiting the CXCL12-mediatedcell migration. This could be one of the underlying mechanisms ofthe CXCL14’s anti-tumor function. We are vigorously investigating
physiological roles of CXCL14 and its action mechanisms. CXCL14 is apromising tool for developing novel anti-cancer and anti-diabetes drugs.

Department of Advanced Science for Biomolecules

Stem Cell60