title: Characterization of TLX expression in neural stem cells and progenitor cells in adult brains.
abstract: TLX has been shown to play an important role in regulating the self-renewal and proliferation of neural stem cells in adult brains. However, the cellular distribution of endogenous TLX protein in adult brains remains to be elucidated. In this study, we used immunostaining with a TLX-specific antibody to show that TLX is expressed in both neural stem cells and transit-amplifying neural progenitor cells in the subventricular zone (SVZ) of adult mouse brains. Then, using a double thymidine analog labeling approach, we showed that almost all of the self-renewing neural stem cells expressed TLX. Interestingly, most of the TLX-positive cells in the SVZ represented the thymidine analog-negative, relatively quiescent neural stem cell population. Using cell type markers and short-term BrdU labeling, we demonstrated that TLX was also expressed in the Mash1+ rapidly dividing type C cells. Furthermore, loss of TLX expression dramatically reduced BrdU label-retaining neural stem cells and the actively dividing neural progenitor cells in the SVZ, but substantially increased GFAP staining and extended GFAP processes. These results suggest that TLX is essential to maintain the self-renewing neural stem cells in the SVZ and that the GFAP+ cells in the SVZ lose neural stem cell property upon loss of TLX expression. Understanding the cellular distribution of TLX and its function in specific cell types may provide insights into the development of therapeutic tools for neurodegenerative diseases by targeting TLX in neural stem/progenitors cells.
authors.affiliation: Department of Neurosciences, Cancer Center, Beckman Research Institute of City of Hope, Duarte, California, United States of America.
authors.forename: Shengxiu
authors.initials: S
authors.lastname: Li
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Sun
authors.forename: Kiyohito
authors.initials: K
authors.lastname: Murai
authors.forename: Peng
authors.initials: P
authors.lastname: Ye
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D001931:Brain Mapping / Q000379:methods; D001973:Bromodeoxyuridine / Q000494:pharmacology; D049109:Cell Proliferation; D005456:Fluorescent Dyes / Q000378:metabolism; D005786:Gene Expression Regulation; D005904:Glial Fibrillary Acidic Protein; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology*; D019636:Neurodegenerative Diseases / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis*; D013234:Stem Cells / Q000166:cytology*; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D005456:Fluorescent Dyes; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; C490258:Nr2e1 protein, mouse; D018160:Receptors, Cytoplasmic and Nuclear; C528900:glial fibrillary astrocytic protein, mouse; D001616:beta-Galactosidase; D001973:Bromodeoxyuridine