scholarly journals EphB4 Regulates Self-Renewal, Proliferation and Neuronal Differentiation of Human Embryonic Neural Stem Cells in Vitro

2017 ◽  
Vol 41 (2) ◽  
pp. 819-834 ◽  
Author(s):  
Tingting Liu ◽  
Xianwei Zeng ◽  
Fangling Sun ◽  
Hongli Hou ◽  
Yunqian Guan ◽  
...  

Background/Aims: EphB4 belongs to the largest family of Eph receptor tyrosine kinases. It contributes to a variety of pathological progresses of cancer malignancy. However, little is known about its role in neural stem cells (NSCs). This study examined whether EphB4 is required for proliferation and differentiation of human embryonic neural stem cells (hNSCs) in vitro. Methods: We up- and down-regulated EphB4 expression in hNSCs using lentiviral over-expression and shRNA knockdown constructs and then investigated the influence of EphB4 on the properties of hNSCs. Results: Our results show that shRNA-mediated EphB4 reduction profoundly impaired hNSCs self-renewal and proliferation. Furthermore, detection of differentiation revealed that knockdown of EphB4 inhibited hNSCs differentiation towards a neuronal lineage and promoted hNSCs differentiation to glial cells. In contrast, EphB4 overexpression promoted hNSCs self-renewal and proliferation, further induced hNSCs differentiation towards a neuronal lineage and inhibited hNSCs differentiation to glial cells. Moreover, we found that EphB4 regulates cell proliferation mediated by the Abl-CyclinD1 pathway. Conclusion: These studies provide strong evidence that fine tuning of EphB4 expression is crucial for the proliferation and neuronal differentiation of hNSCs, suggesting that EphB4 might be an interesting target for overcoming some of the therapeutic limitations of neuronal loss in brain diseases.

Author(s):  
Prithiv K R Kumar

Stem cells have the capacity to differentiate into any type of cell or organ. Stems cell originate from any part of the body, including the brain. Brain cells or rather neural stem cells have the capacitive advantage of differentiating into the central nervous system leading to the formation of neurons and glial cells. Neural stem cells should have a source by editing DNA, or by mixings chemical enzymes of iPSCs. By this method, a limitless number of neuron stem cells can be obtained. Increase in supply of NSCs help in repairing glial cells which in-turn heal the central nervous system. Generally, brain injuries cause motor and sensory deficits leading to stroke. With all trials from novel therapeutic methods to enhanced rehabilitation time, the economy and quality of life is suppressed. Only PSCs have proven effective for grafting cells into NSCs. Neurons derived from stem cells is the only challenge that limits in-vitro usage in the near future.


2021 ◽  
Vol 12 (4) ◽  
pp. 64
Author(s):  
Sahitya Chetan Pandanaboina ◽  
Ambar B. RanguMagar ◽  
Krishna D. Sharma ◽  
Bijay P. Chhetri ◽  
Charlette M. Parnell ◽  
...  

Transplantation of differentiated and fully functional neurons may be a better therapeutic option for the cure of neurodegenerative disorders and brain injuries than direct grafting of neural stem cells (NSCs) that are potentially tumorigenic. However, the differentiation of NSCs into a large population of neurons has been a challenge. Nanomaterials have been widely used as substrates to manipulate cell behavior due to their nano-size, excellent physicochemical properties, ease of synthesis, and versatility in surface functionalization. Nanomaterial-based scaffolds and synthetic polymers have been fabricated with topology resembling the micro-environment of the extracellular matrix. Nanocellulose materials are gaining attention because of their availability, biocompatibility, biodegradability and bioactivity, and affordable cost. We evaluated the role of nanocellulose with different linkage and surface features in promoting neuronal differentiation. Nanocellulose coupled with lysine molecules (CNC–Lys) provided positive charges that helped the cells to attach. Embryonic rat NSCs were differentiated on the CNC–Lys surface for up to three weeks. By the end of the three weeks of in vitro culture, 87% of the cells had attached to the CNC–Lys surface and more than half of the NSCs had differentiated into functional neurons, expressing endogenous glutamate, generating electrical activity and action potentials recorded by the multi-electrode array.


2010 ◽  
Vol 476 (2) ◽  
pp. 74-78 ◽  
Author(s):  
Yang Wang ◽  
Yunqian Guan ◽  
Fang Wang ◽  
Aihua Huang ◽  
Shuyan Wang ◽  
...  

2018 ◽  
Author(s):  
Shiekh Tanveer Ahmad ◽  
Alexandra D. Rogers ◽  
Myra J. Chen ◽  
Rajiv Dixit ◽  
Lata Adnani ◽  
...  

ABSTRACTCapicua (Cic) is a transcriptional repressor mutated in the brain cancer oligodendroglioma. Despite its cancer link, little is known of Cic’s function in the brain. Here, we investigated the relationship between Cic expression and cell type specification in the brain. Cic is strongly expressed in astrocytic and neuronal lineage cells but is more weakly expressed in stem cells and oligodendroglial lineage cells. Using a new conditionalCicknockout mouse, we show that forebrain-specificCicdeletion increases proliferation and self-renewal of neural stem cells. Furthermore,Cicloss biases neural stem cells toward glial lineage selection, expanding the pool of oligodendrocyte precursor cells (OPCs). These proliferation and lineage selection effects in the developing brain are dependent on de-repression of Ets transcription factors. In patient-derived oligodendroglioma cells, CIC re-expression or ETV5 blockade decreases lineage bias, proliferation, self-renewal and tumorigenicity. Our results identify Cic is an important regulator of cell fate in neurodevelopment and oligodendroglioma, and suggest that its loss contributes to oligodendroglioma by promoting proliferation and an OPC-like identity via Ets overactivity.


EMBO Reports ◽  
2021 ◽  
Author(s):  
Zhenming Guo ◽  
Mengxia Chen ◽  
Yiming Chao ◽  
Chunhai Cai ◽  
Liangjie Liu ◽  
...  

Stem Cells ◽  
2006 ◽  
Vol 24 (3) ◽  
pp. 731-738 ◽  
Author(s):  
Gregory P. Marshall ◽  
Eric D. Laywell ◽  
Tong Zheng ◽  
Dennis A. Steindler ◽  
Edward W. Scott

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243644
Author(s):  
Yunfeng Jiang ◽  
Yue Wang ◽  
Yu Sun ◽  
Hong Jiang

Background Exposure to anesthetics during brain development may impair neurological function, however, the mechanisms underlying anesthetic neurotoxicity are unclear. Recent studies indicate that long non-coding RNAs (lncRNAs) are crucial for regulating the functional brain development during neurogenesis. This study aimed to determine the regulatory effects and potential mechanisms of lncRNA Peg13 (Peg13) on sevoflurane exposure-related neurotoxicity against neural stem cells (NSCs). Methods Mouse embryotic NSCs were isolated and their self-renewal and differentiation were characterized by immunofluorescence. NSCs were exposed to 4.1% sevoflurane 2 h daily for three consecutive days. The potential toxicities of sevoflurane against NSCs were evaluated by neurosphere formation, 5-ethynyl-2'-deoxyuridine (EdU) incorporation and flow cytometry assays. The Peg13, miR-128-3p and Sox13 expression in NSCs were quantified. The potential interactions among Peg13, miR-128-3p and Sox13 were analyzed by luciferase reporter assay. The effects of Peg13 and/or miR-128-3p over-expression on the sevoflurane-related neurotoxicity and Sox13 expression were determined in NSCs. Results The isolated mouse embryotic NSCs displayed potent self-renewal ability and differentiated into neurons, astrocytes and oligodendrocytes in vitro, which were significantly inhibited by sevoflurane exposure. Sevoflurane exposure significantly down-regulated Peg13 and Sox13, but enhanced miR-128-3p expression in NSCs. Transfection with miR-128-3p mimics, but not the control, significantly mitigated the Peg13 or Sox13-regulated luciferase expression in 293T cells. Peg13 over-expression significantly reduced the sevoflurane-related neurotoxicity and increased Sox13 expression in NSCs, which were mitigated by miR-128-3p transfection. Conclusion Such data indicated that Peg13 mitigated the sevoflurane-related neurotoxicity by sponging miR-128-3p to preserve Sox13 expression in NSCs.


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