Abstract

Stem cell technology holds great promise for the treatment of a variety of human diseases that currently lack effective therapies. Identifying factors that control stem cell self-renewal is an important step in moving stem cell technology from the laboratory to the clinics. One factor that plays an important role in regulating this process is orphan nuclear receptor TLX. TLX is specifically expressed in mammalian brains and is essential to maintain adult neural stem cells in the undifferentiated and self-renewable state. The objective of this study is to uncover the regulatory cascade of TLX by identifying its downstream target genes and upstream regulators. This study will be critical to the implementation of neural stem cell-based cell replacement therapy for the treatment of neurodegenerative diseases such as Alzheimer's and Parkinson's diseases and brain injuries. The results of this study will provide new insights into TLX signaling pathway and define novel elements that control neural stem cell maintenance and self-renewal. Each component of the TLX signaling network, either downstream target genes or upstream regulators, will be novel molecular targets for intervening neurodegenerative diseases.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS059546-04
Application #
7872777
Study Section
Molecular and Cellular Endocrinology Study Section (MCE)
Program Officer
Owens, David F
Project Start
2007-07-01
Project End
2013-06-30
Budget Start
2010-07-01
Budget End
2013-06-30
Support Year
4
Fiscal Year
2010
Total Cost
$365,991
Indirect Cost

  Institution

Name
City of Hope/Beckman Research Institute
Department
Type
DUNS #
027176833
City
Duarte
State
CA
Country
United States
Zip Code
91010

  Publications

Tuoc, Tran; Dere, Ekrem; Radyushkin, Konstantin et al. (2017) Ablation of BAF170 in Developing and Postnatal Dentate Gyrus Affects Neural Stem Cell Proliferation, Differentiation, and Learning. Mol Neurobiol 54:4618-4635
Murai, Kiyohito; Qu, Qiuhao; Sun, GuoQiang et al. (2014) Nuclear receptor TLX stimulates hippocampal neurogenesis and enhances learning and memory in a transgenic mouse model. Proc Natl Acad Sci U S A 111:9115-20
Zhang, Run-Rui; Cui, Qing-Yan; Murai, Kiyohito et al. (2013) Tet1 regulates adult hippocampal neurogenesis and cognition. Cell Stem Cell 13:237-45
Qu, Qiuhao; Sun, Guoqiang; Murai, Kiyohito et al. (2013) Wnt7a regulates multiple steps of neurogenesis. Mol Cell Biol 33:2551-9
Zhao, Chunnian; Sun, GuoQiang; Ye, Peng et al. (2013) MicroRNA let-7d regulates the TLX/microRNA-9 cascade to control neural cell fate and neurogenesis. Sci Rep 3:1329
Asuelime, Grace E; Shi, Yanhong (2012) The little molecules that could: a story about microRNAs in neural stem cells and neurogenesis. Front Neurosci 6:176
Asuelime, Grace E; Shi, Yanhong (2012) A case of cellular alchemy: lineage reprogramming and its potential in regenerative medicine. J Mol Cell Biol 4:190-6
Lang, Ming-Fei; Shi, Yanhong (2012) Dynamic Roles of microRNAs in Neurogenesis. Front Neurosci 6:71
Lang, Ming-Fei; Yang, Su; Zhao, Chunnian et al. (2012) Genome-wide profiling identified a set of miRNAs that are differentially expressed in glioblastoma stem cells and normal neural stem cells. PLoS One 7:e36248
Li, Shengxiu; Sun, Guoqiang; Murai, Kiyohito et al. (2012) Characterization of TLX expression in neural stem cells and progenitor cells in adult brains. PLoS One 7:e43324

Showing the most recent 10 out of 24 publications