scholarly journals Impaired generation of mature neurons by neural stem cells from hypomorphic Sox2 mutants

Development ◽  
2008 ◽  
Vol 135 (3) ◽  
pp. 541-557 ◽  
Author(s):  
M. Cavallaro ◽  
J. Mariani ◽  
C. Lancini ◽  
E. Latorre ◽  
R. Caccia ◽  
...  
Development ◽  
2017 ◽  
Vol 144 (21) ◽  
pp. 3968-3977 ◽  
Author(s):  
Stéphane Bugeon ◽  
Antoine de Chevigny ◽  
Camille Boutin ◽  
Nathalie Coré ◽  
Stefan Wild ◽  
...  

Stem Cells ◽  
2012 ◽  
Vol 30 (12) ◽  
pp. 2657-2671 ◽  
Author(s):  
Carlo Cusulin ◽  
Emanuela Monni ◽  
Henrik Ahlenius ◽  
James Wood ◽  
Jan Claas Brune ◽  
...  

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Ana Marin Navarro ◽  
Robin Johan Pronk ◽  
Astrid Tjitske van der Geest ◽  
Ganna Oliynyk ◽  
Ann Nordgren ◽  
...  

AbstractIn this study, we take advantage of human induced pluripotent stem (iPS) cell-derived neural stem cells and brain organoids to study the role of p53 during human brain development. We knocked down (KD) p53 in human neuroepithelial stem (NES) cells derived from iPS cells. Upon p53KD, NES cells rapidly show centrosome amplification and genomic instability. Furthermore, a reduced proliferation rate, downregulation of genes involved in oxidative phosphorylation (OXPHOS), and an upregulation of glycolytic capacity was apparent upon loss of p53. In addition, p53KD neural stem cells display an increased pace of differentiating into neurons and exhibit a phenotype corresponding to more mature neurons compared to control neurons. Using brain organoids, we modeled more specifically cortical neurogenesis. Here we found that p53 loss resulted in brain organoids with disorganized stem cell layer and reduced cortical progenitor cells and neurons. Similar to NES cells, neural progenitors isolated from brain organoids also show a downregulation in several OXPHOS genes. Taken together, this demonstrates an important role for p53 in controlling genomic stability of neural stem cells and regulation of neuronal differentiation, as well as maintaining structural organization and proper metabolic gene profile of neural progenitors in human brain organoids.


2021 ◽  
Vol 4 (1) ◽  
pp. 23-41
Author(s):  
Alexandra-Elena Dobranici ◽  
Sorina Dinescu ◽  
Marieta Costache

Specialised cells of the brain are generated from a population of multipotent stem cells found in the forming embryo and adult brain after birth, called neural stem cells. They reside in specific niches, usually in a quiescent, non-proliferating state that maintains their reservoir. Neural stem cells are kept inactive by various cues such as direct cell-cell contacts with neighbouring cells or by soluble molecules that trigger intracellular responses. They are activated in response to injuries, physical exercise, or hypoxia condition, through stimulation of signaling pathways that are usually correlated with increased proliferation and survival. Moreover, mature neurons play essential role in regulating the balance between active and quiescent state by realising inhibitory or activating neurotransmitters. Understanding molecular mechanisms underlying neuronal differentiation is of great importance in elucidating pathological conditions of the brain and treating neurodegenerative disorders that until now have no efficient therapies.


Stem Cells ◽  
2015 ◽  
Vol 33 (12) ◽  
pp. 3530-3544 ◽  
Author(s):  
Stuart L. Gibb ◽  
Yuhai Zhao ◽  
Daniel Potter ◽  
Michael J. Hylin ◽  
Roberta Bruhn ◽  
...  

2017 ◽  
Vol 53 (80) ◽  
pp. 11024-11027 ◽  
Author(s):  
Fu-Yu Hsieh ◽  
Lok Kumar Shrestha ◽  
Katsuhiko Ariga ◽  
Shan-hui Hsu

Highly-aligned fullerene nanowhiskers (C60 NWs) are prepared by a modified liquid–liquid interfacial precipitation method. Neural stem cells on the aligned C60 NWs are oriented and have a high capacity to differentiate into mature neurons.


2004 ◽  
Vol 24 (18) ◽  
pp. 8018-8025 ◽  
Author(s):  
Xiaohua Su ◽  
Sei Kameoka ◽  
Susan Lentz ◽  
Sadhan Majumder

ABSTRACT REST/NRSF is a transcriptional repressor that acts at the terminal stage of the neuronal differentiation pathway and blocks the transcription of several differentiation genes. REST/NRSF is generally downregulated during induction of neuronal differentiation. The recombinant transcription factor REST-VP16 binds to the same DNA binding site as does REST/NRSF but functions as an activator instead of a repressor and can directly activate the transcription of REST/NRSF target genes. However, it is not known whether REST-VP16 expression is sufficient to cause formation of functional neurons from neural stem cells (NSCs). Here we show that regulated expression of REST-VP16 in a physiologically relevant NSC line growing under cycling conditions converted the cells rapidly to the mature neuronal phenotype. Furthermore, when grown in the presence of retinoic acid, REST-VP16-expressing NSCs activated their target, as well as other differentiation genes that are not their direct target, converting them to the mature neuronal phenotype and enabling them to survive in the presence of mitotic inhibitors, which is a characteristic of mature neurons. In addition, these neuronal cells were physiologically active. These results showed that direct activation of REST/NRSF target genes in NSCs with a single transgene, REST-VP16, is sufficient to cause neuronal differentiation, and the findings suggested that direct activation of genes involved in the terminal stage of differentiation may cause neuronal differentiation of NSCs.


Stem Cells ◽  
2021 ◽  
Author(s):  
Çağla Defteralı ◽  
Mireia Moreno-Estellés ◽  
Carlos Crespo ◽  
Eva Díaz-Guerra ◽  
María Díaz-Moreno ◽  
...  

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Limin Wang ◽  
Feng He ◽  
Zhuoyuan Zhong ◽  
Ruiyan Lv ◽  
Songhua Xiao ◽  
...  

Neurotrophic tyrosine kinase type 1 (NTRK1) plays critical roles in proliferation, differentiation, and survival of cholinergic neurons; however, it remains unknown whether enhanced expression of NTRK1 in neural stem cells (NSCs) can promote their differentiation into mature neurons. In this study, a plasmid encoding the rat NTRK1 gene was constructed and transfected into C17.2 mouse neural stem cells (NSCs). NTRK1 overexpression in C17.2 cells was confirmed by western blot. The NSCs overexpressing NTRK1 and the C17.2 NSCs transfected by an empty plasmid vector were treated with or without 100 ng/mL nerve growth factor (NGF) for 7 days. Expression of the cholinergic cell marker, choline acetyltransferase (ChAT), was detected by florescent immunocytochemistry (ICC). In the presence of NGF induction, the NSCs overexpressing NTRK1 differentiated into ChAT-immunopositive cells at 3-fold higher than the NSCs transfected by the plasmid vector (26% versus 9%,P<0.05). The data suggest that elevated NTRK1 expression increases differentiation of NSCs into cholinergic neurons under stimulation of NGF. The approach also represents an efficient strategy for generation of cholinergic neurons.


Sign in / Sign up

Export Citation Format

Share Document