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@ARTICLE{Lupo:134832,
author = {G. Lupo and P. S. Nisi and P. Esteve and Y.-L. Paul and C.
L. Novo and B. Sidders and M. A. Khan$^*$ and S. Biagioni
and H.-K. Liu$^*$ and P. Bovolenta and E. Cacci and P. J.
Rugg-Gunn},
title = {{M}olecular profiling of aged neural progenitors identifies
{D}bx2 as a candidate regulator of age-associated neurogenic
decline.},
journal = {Aging cell},
volume = {17},
number = {3},
issn = {1474-9718},
address = {Oxford [u.a.]},
publisher = {Wiley-Blackwell},
reportid = {DKFZ-2018-00622},
pages = {e12745 -},
year = {2018},
note = {DKFZ-ZMBH-Allianz},
abstract = {Adult neurogenesis declines with aging due to the depletion
and functional impairment of neural stem/progenitor cells
(NSPCs). An improved understanding of the underlying
mechanisms that drive age-associated neurogenic deficiency
could lead to the development of strategies to alleviate
cognitive impairment and facilitate neuroregeneration. An
essential step towards this aim is to investigate the
molecular changes that occur in NSPC aging on a genomewide
scale. In this study, we compare the transcriptional,
histone methylation and DNA methylation signatures of NSPCs
derived from the subventricular zone (SVZ) of young adult
(3 months old) and aged (18 months old) mice.
Surprisingly, the transcriptional and epigenomic profiles of
SVZ-derived NSPCs are largely unchanged in aged cells.
Despite the global similarities, we detect robust
age-dependent changes at several hundred genes and
regulatory elements, thereby identifying putative regulators
of neurogenic decline. Within this list, the homeobox gene
Dbx2 is upregulated in vitro and in vivo, and its promoter
region has altered histone and DNA methylation levels, in
aged NSPCs. Using functional in vitro assays, we show that
elevated Dbx2 expression in young adult NSPCs promotes
age-related phenotypes, including the reduced proliferation
of NSPC cultures and the altered transcript levels of
age-associated regulators of NSPC proliferation and
differentiation. Depleting Dbx2 in aged NSPCs caused the
reverse gene expression changes. Taken together, these
results provide new insights into the molecular programmes
that are affected during mouse NSPC aging, and uncover a new
functional role for Dbx2 in promoting age-related neurogenic
decline.},
cin = {A240},
ddc = {610},
cid = {I:(DE-He78)A240-20160331},
pnm = {311 - Signalling pathways, cell and tumor biology
(POF3-311)},
pid = {G:(DE-HGF)POF3-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29504228},
pmc = {pmc:PMC5946077},
doi = {10.1111/acel.12745},
url = {https://inrepo02.dkfz.de/record/134832},
}