scholarly journals Faculty Opinions recommendation of Neuronal differentiation and cell-cycle programs mediate response to BET-bromodomain inhibition in MYC-driven medulloblastoma.

Author(s):  
Jason Huse
2019 ◽  
Vol 21 (Supplement_2) ◽  
pp. ii111-ii111
Author(s):  
Pratiti Bandopadhayay ◽  
Federica Piccioni ◽  
Ryan O’Rourke ◽  
Patricia Ho ◽  
Elizabeth Gonzalez ◽  
...  

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Pratiti Bandopadhayay ◽  
Federica Piccioni ◽  
Ryan O’Rourke ◽  
Patricia Ho ◽  
Elizabeth M. Gonzalez ◽  
...  

2021 ◽  
Vol 22 (14) ◽  
pp. 7566
Author(s):  
Eleonora Stronati ◽  
Stefano Biagioni ◽  
Mario Fiore ◽  
Mauro Giorgi ◽  
Giancarlo Poiana ◽  
...  

Nervous system development involves proliferation and cell specification of progenitor cells into neurons and glial cells. Unveiling how this complex process is orchestrated under physiological conditions and deciphering the molecular and cellular changes leading to neurological diseases is mandatory. To date, great efforts have been aimed at identifying gene mutations associated with many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Mutations in the RNA/DNA binding protein Fused in Sarcoma/Translocated in Liposarcoma (FUS/TLS) have been associated with motor neuron degeneration in rodents and humans. Furthermore, increased levels of the wild-type protein can promote neuronal cell death. Despite the well-established causal link between FUS mutations and ALS, its role in neural cells remains elusive. In order to shed new light on FUS functions we studied its role in the control of neural stem progenitor cell (NSPC) properties. Here, we report that human wild-type Fused in Sarcoma (WT FUS), exogenously expressed in mouse embryonic spinal cord-derived NSPCs, was localized in the nucleus, caused cell cycle arrest in G1 phase by affecting cell cycle regulator expression, and strongly reduced neuronal differentiation. Furthermore, the expression of the human mutant form of FUS (P525L-FUS), associated with early-onset ALS, drives the cells preferentially towards a glial lineage, strongly reducing the number of developing neurons. These results provide insight into the involvement of FUS in NSPC proliferation and differentiation into neurons and glia.


2007 ◽  
Vol 73 (2) ◽  
pp. 498-508 ◽  
Author(s):  
Laura Papucci ◽  
Ewa Witort ◽  
Anna Maria Bevilacqua ◽  
Martino Donnini ◽  
Matteo Lulli ◽  
...  

2011 ◽  
Vol 301 (3) ◽  
pp. R727-R745 ◽  
Author(s):  
Hady Felfly ◽  
Jin Xue ◽  
Alexander C. Zambon ◽  
Alysson Muotri ◽  
Dan Zhou ◽  
...  

Stem cells are a potential key strategy for treating neurodegenerative diseases in which the generation of new neurons is critical. A better understanding of the characteristics and molecular properties of neural stem cells (NSCs) and differentiated neurons can help with assessing neuronal maturity and, possibly, in devising better therapeutic strategies. We have performed an in-depth gene expression profiling study of murine NSCs and primary neurons derived from embryonic mouse brains. Microarray analysis revealed a neuron-specific gene expression signature that distinguishes primary neurons from NSCs, with elevated levels of transcripts involved in neuronal functions, such as neurite development and axon guidance in primary neurons and decreased levels of multiple cytokine transcripts. Among the differentially expressed genes, we found a statistically significant enrichment of genes in the ephrin, neurotrophin, CDK5, and actin pathways, which control multiple neuronal-specific functions. We then artificially blocked the cell cycle of NSCs with mitomycin C (MMC) and examined cellular morphology and gene expression signatures. Although these MMC-treated NSCs displayed a neuronal morphology and expressed some neuronal differentiation marker genes, their gene expression patterns were very different from primary neurons. We conclude that 1) fully differentiated mouse primary neurons display a specific neuronal gene expression signature; 2) cell cycle block at the S phase in NSCs with MMC does not induce the formation of fully differentiated neurons; 3) cytokines change their expression pattern during differentiation of NSCs into neurons; and 4) signaling pathways of ephrin, neurotrophin, CDK5, and actin, related to major neuronal features, are dynamically enriched in genes showing changes in expression level.


RSC Advances ◽  
2016 ◽  
Vol 6 (21) ◽  
pp. 16972-16981 ◽  
Author(s):  
Ling Wang ◽  
Yecheng Li ◽  
Mengyan Xu ◽  
Xiaoqian Pang ◽  
Zhihong Liu ◽  
...  

Cyclin-dependent kinases (CDKs), a family of mammalian heterodimeric kinases, play central roles in the regulation of cell cycle progression, transcription, neuronal differentiation, and metabolism.


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