TY - JOUR
T1 - Overexpression of cdk4 and cyclinD1 triggers greater expansion of neural stem cells in the adult mouse brain
AU - Artegiani, Benedetta
AU - Lindemann, Dirk
AU - Calegari, Federico
PY - 2011/5/9
Y1 - 2011/5/9
N2 - Neural stem cells (NSCs) in the adult mammalian brain generate neurons and glia throughout life. However, the physiological role of adult neurogenesis and the use of NSCs for therapy are highly controversial. One factor hampering the study and manipulation of neurogenesis is that NSCs, like most adult somatic stem cells, are difficult to expand and their switch to differentiation is hard to control. In this study, we show that acute overexpression of the cdk4 (cyclin-dependent kinase 4)-cyclinD1 complex in the adult mouse hippocampus cell-autonomously increases the expansion of neural stem and progenitor cells while inhibiting neurogenesis. Importantly, we developed a system that allows the temporal control of cdk4-cyclinD1 overexpression, which can be used to increase the number of neurons generated from the pool of manipulated precursor cells. Beside providing a proof of principle that expansion versus differentiation of somatic stem cells can be controlled in vivo, our study describes, to the best of our knowledge, the first acute and inducible temporal control of neurogenesis in the mammalian brain, which may be critical for identifying the role of adult neurogenesis, using NSCs for therapy, and, perhaps, extending our findings to other adult somatic stem cells.
AB - Neural stem cells (NSCs) in the adult mammalian brain generate neurons and glia throughout life. However, the physiological role of adult neurogenesis and the use of NSCs for therapy are highly controversial. One factor hampering the study and manipulation of neurogenesis is that NSCs, like most adult somatic stem cells, are difficult to expand and their switch to differentiation is hard to control. In this study, we show that acute overexpression of the cdk4 (cyclin-dependent kinase 4)-cyclinD1 complex in the adult mouse hippocampus cell-autonomously increases the expansion of neural stem and progenitor cells while inhibiting neurogenesis. Importantly, we developed a system that allows the temporal control of cdk4-cyclinD1 overexpression, which can be used to increase the number of neurons generated from the pool of manipulated precursor cells. Beside providing a proof of principle that expansion versus differentiation of somatic stem cells can be controlled in vivo, our study describes, to the best of our knowledge, the first acute and inducible temporal control of neurogenesis in the mammalian brain, which may be critical for identifying the role of adult neurogenesis, using NSCs for therapy, and, perhaps, extending our findings to other adult somatic stem cells.
KW - Animals
KW - Cyclin D1/biosynthesis
KW - Cyclin-Dependent Kinase 4/biosynthesis
KW - Gene Expression Regulation/physiology
KW - HeLa Cells
KW - Hippocampus/cytology
KW - Humans
KW - Mice
KW - Neural Stem Cells/metabolism
KW - Neurogenesis/physiology
UR - http://www.scopus.com/inward/record.url?scp=79956125698&partnerID=8YFLogxK
U2 - 10.1084/jem.20102167
DO - 10.1084/jem.20102167
M3 - Article
C2 - 21482697
SN - 0022-1007
VL - 208
SP - 937
EP - 948
JO - The Journal of experimental medicine
JF - The Journal of experimental medicine
IS - 5
ER -