Neural Stem Cells

Publication Title: 
PloS One

BACKGROUND: Mutation in the ubiquitously expressed cytoplasmic superoxide dismutase (SOD1) causes an inherited form of Amyotrophic Lateral Sclerosis (ALS). Mutant synthesis in motor neurons drives disease onset and early disease progression. Previous experimental studies have shown that spinal grafting of human fetal spinal neural stem cells (hNSCs) into the lumbar spinal cord of SOD1(G93A) rats leads to a moderate therapeutical effect as evidenced by local ?-motoneuron sparing and extension of lifespan.

Author(s): 
Hefferan, Michael P.
Galik, Jan
Kakinohana, Osamu
Sekerkova, Gabriela
Santucci, Camila
Marsala, Silvia
Navarro, Roman
Hruska-Plochan, Marian
Johe, Karl
Feldman, Eva
Cleveland, Don W.
Marsala, Martin
Publication Title: 
Aging Cell

The contribution that oxidative damage to DNA and/or RNA makes to the aging process remains undefined. In this study, we used the hMTH1-Tg mouse model to investigate how oxidative damage to nucleic acids affects aging. hMTH1-Tg mice express high levels of the hMTH1 hydrolase that degrades 8-oxodGTP and 8-oxoGTP and excludes 8-oxoguanine from both DNA and RNA. Compared to wild-type animals, hMTH1-overexpressing mice have significantly lower steady-state levels of 8-oxoguanine in both nuclear and mitochondrial DNA of several organs, including the brain.

Author(s): 
De Luca, Gabriele
Ventura, Ilenia
Sanghez, Valentina
Russo, Maria Teresa
Ajmone-Cat, Maria Antonietta
Cacci, Emanuele
Martire, Alberto
Popoli, Patrizia
Falcone, Germana
Michelini, Flavia
Crescenzi, Marco
Degan, Paolo
Minghetti, Luisa
Bignami, Margherita
Calamandrei, Gemma
Publication Title: 
MÈdecine Sciences: M/S

Most of the signalling pathways involved in aging regulation have been recently found well conserved at various levels throughout the evolution. Taking this into account, a diversity of model organisms, including worms, rodents, and lemurs as well, allows to address different questions: how to understand the interactions between genetic and environmental factors while challenging theories of aging, to preserve hearing integrity, to fight against senescence of neural stem cells, or to explore brain fitness from gene expression to cognitive and social behavior?

Author(s): 
Galas, Simon
Ch‚teau, Marie-ThÈrËse
PomiËs, Pascal
Wang, Jing
Menardo, Julien
Puel, Jean-Luc
Hugnot, Jean-Philippe
Verdier, Jean-Michel
Devau, Gina
Publication Title: 
Aging Cell

The contribution that oxidative damage to DNA and/or RNA makes to the aging process remains undefined. In this study, we used the hMTH1-Tg mouse model to investigate how oxidative damage to nucleic acids affects aging. hMTH1-Tg mice express high levels of the hMTH1 hydrolase that degrades 8-oxodGTP and 8-oxoGTP and excludes 8-oxoguanine from both DNA and RNA. Compared to wild-type animals, hMTH1-overexpressing mice have significantly lower steady-state levels of 8-oxoguanine in both nuclear and mitochondrial DNA of several organs, including the brain.

Author(s): 
De Luca, Gabriele
Ventura, Ilenia
Sanghez, Valentina
Russo, Maria Teresa
Ajmone-Cat, Maria Antonietta
Cacci, Emanuele
Martire, Alberto
Popoli, Patrizia
Falcone, Germana
Michelini, Flavia
Crescenzi, Marco
Degan, Paolo
Minghetti, Luisa
Bignami, Margherita
Calamandrei, Gemma
Publication Title: 
Stem Cells (Dayton, Ohio)

Monoallelic gene expression, such as genomic imprinting, is well described. Less well-characterized are genes undergoing stochastic monoallelic expression (MA), where specific clones of cells express just one allele at a given locus. We performed genome-wide allelic expression assessment of human clonal neural stem cells derived from cerebral cortex, striatum, and spinal cord, each with differing genotypes. We assayed three separate clonal lines from each donor, distinguishing stochastic MA from genotypic effects.

Author(s): 
Jeffries, Aaron R.
Perfect, Leo W.
Ledderose, Julia
Schalkwyk, Leonard C.
Bray, Nicholas J.
Mill, Jonathan
Price, Jack
Publication Title: 
International Journal of Molecular Sciences

Schizophrenia is a complex genetic disease and characterized by affective, cognitive, neuromorphological, and molecular abnormalities that may have a neurodevelopmental origin. MicroRNAs (miRNAs) are critical to neurodevelopment and adult neuronal processes by modulating the activity of multiple genes within biological networks. MiR-137 as a brain-enriched microRNA, plays important roles in regulating embryonic neural stem cells (NSCs) fate determination, neuronal proliferation and differentiation, and synaptic maturation.

Author(s): 
Yin, Jingwen
Lin, Juda
Luo, Xudong
Chen, Yanyan
Li, Zheng
Ma, Guoda
Li, Keshen
Publication Title: 
Biological Psychiatry

Neurodegenerative disorders of aging represent a growing public health concern. In the United States alone, there are now >5 million patients with Alzheimer's disease (AD), the most common form of dementia. No therapeutic approaches are available that alter the relentless course of AD or other dementias of aging. A major hurdle to the development of effective therapeutics has been the lack of predictive model systems in which to develop and validate candidate therapies.

Author(s): 
Doege, Claudia A.
Abeliovich, Asa
Publication Title: 
Stem Cells Translational Medicine

Recent advances in somatic cell reprogramming have highlighted the plasticity of the somatic epigenome, particularly through demonstrations of direct lineage reprogramming of adult mouse and human fibroblasts to induced pluripotent stem cells (iPSCs) and induced neurons (iNs) under defined conditions. However, human cells appear to be less plastic and have a higher epigenetic hurdle for reprogramming to both iPSCs and iNs. Here, we show that SH2B adaptor protein 1?

Author(s): 
Hsu, Yi-Chao
Chen, Su-Liang
Wang, Ya-Jean
Chen, Yun-Hsiang
Wang, Dan-Yen
Chen, Linyi
Chen, Chia-Hsiang
Chen, Hwei-Hsien
Chiu, Ing-Ming
Publication Title: 
Epigenomics

Imprinted genes and neural stem cells (NSC) play an important role in the developing and mature brain. A central theme of imprinted gene function in NSCs is cell survival and G1 arrest to control cell division, cell-cycle exit, migration and differentiation. Moreover, genomic imprinting can be epigenetically switched off at some genes to ensure stem cell quiescence and differentiation. At the genome scale, imprinted genes are organized in dynamic networks formed by interchromosomal interactions and transcriptional coregulation of imprinted and nonimprinted genes.

Author(s): 
Hoffmann, Anke
Daniel, Guillaume
Schmidt-Edelkraut, Udo
Spengler, Dietmar
Publication Title: 
Translational Psychiatry

The genetic and epigenetic factors contributing to risk for schizophrenia (SZ) remain unresolved. Here we demonstrate, for the first time, perturbed global protein translation in human-induced pluripotent stem cell (hiPSC)-derived forebrain neural progenitor cells (NPCs) from four SZ patients relative to six unaffected controls.

Author(s): 
Topol, A.
English, J. A.
Flaherty, E.
Rajarajan, P.
Hartley, B. J.
Gupta, S.
Desland, F.
Zhu, S.
Goff, T.
Friedman, L.
Rapoport, J.
Felsenfeld, D.
Cagney, G.
Mackay-Sim, A.
Savas, J. N.
Aronow, B.
Fang, G.
Zhang, B.
Cotter, D.
Brennand, K. J.

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