scholarly journals Omega-3 Polyunsaturated Fatty Acids Enhance Neuronal Differentiation in Cultured Rat Neural Stem Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Masanori Katakura ◽  
Michio Hashimoto ◽  
Toshiyuki Okui ◽  
Hossain Md Shahdat ◽  
Kentaro Matsuzaki ◽  
...  

Polyunsaturated fatty acids (PUFAs) can induce neurogenesis and recovery from brain diseases. However, the exact mechanisms of the beneficial effects of PUFAs have not been conclusively described. We recently reported that docosahexaenoic acid (DHA) induced neuronal differentiation by decreasing Hes1 expression and increasingp27kip1expression, which causes cell cycle arrest in neural stem cells (NSCs). In the present study, we examined the effect of eicosapentaenoic acid (EPA) and arachidonic acid (AA) on differentiation, expression of basic helix-loop-helix transcription factors (Hes1, Hes6, and NeuroD), and the cell cycle of cultured NSCs. EPA also increased mRNA levels of Hes1, an inhibitor of neuronal differentiation, Hes6, an inhibitor of Hes1, NeuroD, and Map2 mRNA and Tuj-1-positive cells (a neuronal marker), indicating that EPA induced neuronal differentiation. EPA increased the mRNA levels ofp21cip1andp27kip1, a cyclin-dependent kinase inhibitor, which indicated that EPA induced cell cycle arrest. Treatment with AA decreased Hes1 mRNA but did not affect NeuroD and Map2 mRNA levels. Furthermore, AA did not affect the number of Tuj-1-positive cells or cell cycle progression. These results indicated that EPA could be involved in neuronal differentiation by mechanisms alternative to those of DHA, whereas AA did not affect neuronal differentiation in NSCs.

Life Sciences ◽  
2018 ◽  
Vol 209 ◽  
pp. 34-42 ◽  
Author(s):  
Shiwen Liu ◽  
Fang Fang ◽  
Ruixue Song ◽  
Xuan Gao ◽  
Ming Jiang ◽  
...  

2021 ◽  
Author(s):  
Elli Marinopoulou ◽  
Nitin Sabherwal ◽  
Veronica Biga ◽  
Jayni Desai ◽  
Antony D. Adamson ◽  
...  

SummaryQuiescence is a dynamic process of reversible cell-cycle arrest. High-level sustained expression of the HES1 transcriptional repressor, which oscillates with an ultradian periodicity in proliferative neural stem cells (NSCs), is thought to mediate quiescence. However, it is not known whether this is due to a change in levels or in dynamics. Here, we induce quiescence in NSCs with BMP4, which does not increase HES1 level, and we find that HES1 continues to oscillate. To assess the role of HES1 dynamics, we express sustained HES1 under a moderate-strength promoter, which overrides the endogenous oscillations while maintaining the total HES1 level within physiological range. We find that sustained HES1 does not affect proliferation or entry into quiescence, however, exit from quiescence is impeded. Thus, oscillatory expression of HES1 is specifically required for NSCs to exit quiescence, a finding of potential importance for controlling reactivation of stem cells in tissue regeneration and cancer.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jiongjia Cheng ◽  
John R. Cashman

Abstract Today, pancreatic cancer (PC) remains a major health problem in the US. The fact that cancer stem cells (CSCs) become enriched in humans following anti-cancer therapy implicates CSCs as key contributors to tumor dormancy, metastasis, and relapse in PC. A highly validated CSC model (FGβ3 cells) was used to test a novel compound (PAWI-2) to eradicate CSCs. Compared to parental bulk FG cells, PAWI-2 showed greater potency to inhibit cell viability and self-renewal capacity of FGβ3 cells. For FGβ3 cells, dysregulated integrin β3-KRAS signaling drives tumor progression. PAWI-2 inhibited β3-KRAS signaling independent of KRAS. This is clinically relevant. PAWI-2 targeted the downstream TBK1 phosphorylation cascade that was negatively regulated by optineurin phosphorylation via a feedback mechanism. This was confirmed by TBK1 genetic knockdown or co-treatment with TBK1-specific inhibitor (MRT67307). PAWI-2 also overcame erlotinib (an EGFR inhibitor) resistance in FGβ3 cells more potently than bortezomib. In the proposed working model, optineurin acts as a key regulator to link inhibition of KRAS signaling and cell cycle arrest (G2/M). The findings show PAWI-2 is a new approach to reverse tumor stemness that resensitizes CSC tumors to drug inhibition.


2017 ◽  
Vol 21 (1) ◽  
pp. 107-119.e6 ◽  
Author(s):  
Phong Dang Nguyen ◽  
David Baruch Gurevich ◽  
Carmen Sonntag ◽  
Lucy Hersey ◽  
Sara Alaei ◽  
...  

Stem Cells ◽  
2020 ◽  
Vol 38 (5) ◽  
pp. 613-623
Author(s):  
Suveg Pandey ◽  
Kelly M. Banks ◽  
Ritu Kumar ◽  
Andrew Kuo ◽  
Duancheng Wen ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document