Transient Induction of RET Activity Pushes CNS Neural Stem Cells Towards Enteric Phenotype Through Activation of Multiple Signaling Pathways

Hyperbaric oxygen (HBO) therapy may promote neurological recovery from hypoxic-ischemic encephalopathy (HIE). However, the therapeutic effects of HBO and its associated mechanisms remain unknown. The canonical Wnt/β-catenin signaling pathways and bone morphogenetic protein (BMP) play important roles in mammalian nervous system development. The present study examined whether HBO stimulates the differentiation of neural stem cells (NSCs) and its effect on Wnt3/β-catenin and BMP2 signaling pathways. We showed HBO treatment (2 ATA, 60 min) promoted differentiation of NSCs into neurons and oligodendrocytes in vitro. In addition, rat hypoxic-ischemic brain damage (HIBD) tissue extracts also promoted the differentiation of NSCs into neurons and oligodendrocytes, with the advantage of reducing the number of astrocytes. These effects were most pronounced when these two were combined together. In addition, the expression of Wnt3a, BMP2, and β-catenin nuclear proteins were increased after HBO treatment. However, blockade of Wnt/β-catenin or BMP signaling inhibited NSC differentiation and reduced the expression of Wnt3a, BMP2, and β-catenin nuclear proteins. In conclusion, HBO promotes differentiation of NSCs into neurons and oligodendrocytes and reduced the number of astrocytes in vitro possibly through regulation of Wnt3/β-catenin and BMP2 signaling pathways. HBO may serve as a potential therapeutic strategy for treating HIE.

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Protein signaling pathways in differentiation of neural stem cells

PROTEOMICS ◽

10.1002/pmic.200800096 ◽

2008 ◽

Vol 8 (21) ◽

pp. 4547-4559 ◽

Cited By ~ 15

Author(s):

Helena Skalnikova ◽

Petr Vodicka ◽

Steven Pelech ◽

Jan Motlik ◽

Suresh Jivan Gadher ◽

...

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Signaling Pathways ◽

Protein Signaling

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Natural Products Targeting Cancer Stem Cells for Augmenting Cancer Therapeutics

International Journal of Molecular Sciences ◽

10.3390/ijms222313044 ◽

2021 ◽

Vol 22 (23) ◽

pp. 13044

Author(s):

Ari Meerson ◽

Soliman Khatib ◽

Jamal Mahajna

Keyword(s):

Stem Cells ◽

Natural Products ◽

Cancer Stem Cells ◽

Signaling Pathways ◽

Tumor Cells ◽

Cancer Therapeutics ◽

Chemotherapeutic Agents ◽

Biologically Active ◽

Approved Drugs ◽

Multiple Signaling

Cancer stem cells (CSC) have been identified in several types of solid tumors. In some cases, CSC may be the source of all the tumor cells, the cause of the tumor’s resistance to chemotherapeutic agents, and the source of metastatic cells. Thus, a combination therapy targeting non-CSC tumor cells as well as specifically targeting CSCs holds the potential to be highly effective. Natural products (NPs) have been a historically rich source of biologically active compounds and are known for their ability to influence multiple signaling pathways simultaneously with negligible side effects. In this review, we discuss the potential of NPs in targeting multiple signaling pathways in CSC and their potential to augment the efficacy of standard cancer therapy. Specifically, we focus on the anti-CSC activities of flavonoids, FDA-approved drugs originating from natural sources. Additionally, we emphasize the potential of NPs in targeting microRNA-mediated signaling, given the roles of microRNA in the maintenance of the CSC phenotype.

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Resolving the transcriptional transitions associated with oligodendrocyte generation from adult neural stem cells by single cell sequencing

10.1101/2020.12.18.423285 ◽

2020 ◽

Author(s):

Kasum Azim ◽

Filippo Calzolari ◽

Martina Cantone ◽

Rainer Akkermann ◽

Julio Vera ◽

...

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Single Cell ◽

Signaling Pathways ◽

Regulatory Control ◽

Transcriptional Networks ◽

Detailed Knowledge ◽

List Type ◽

Specific Expression ◽

Gene Regulatory

AbstractThe subventricular zone (SVZ) is the largest neurogenic niche in the adult forebrain. Notably, neural stem cells (NSCs) of the SVZ generate not only neurons, but also oligodendrocytes, the myelin-forming cells of the central nervous system. Transcriptomic studies have provided detailed knowledge of the molecular events that regulate neurogenesis, but little is understood about adult oligodendrogenesis from SVZ-NSCs. To address this, we performed in-depth single-cell transcriptomic analyses to resolve the major differences in neuronal and oligodendroglial lineages derived from the adult SVZ. A hallmark of adult oligodendrogenesis was the stage-specific expression of transcriptional modulators that regulate developmental oligodendrogenesis. Notably, divergence of the oligodendroglial lineage was distinguished by Wnt-Notch and angiogenesis-related signaling, whereas G-protein-coupled receptor signaling pathways were the major signature observed in the neurogenic lineage. Moreover, in-depth gene regulatory network analysis identified key stage-specific master regulators of the oligodendrocyte lineage and revealed new mechanisms by which signaling pathways interact with transcriptional networks to control lineage progression. Our work provides an integrated view of the multi-step differentiation process leading from NSCs to mature oligodendrocytes, by linking environmental signals to known and novel transcriptional mechanisms orchestrating oligodendrogenesis.Main pointsDistinct adult NSC populations giving rise to either oligodendrocytes or neurons can be identified by the expression of transcription factors.Gene regulatory control of oligodendrogenesis is a major fate-determinant for their generation.

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Comparison of the Gene Expression Profiles of Human Fetal Cortical Astrocytes with Pluripotent Stem Cell Derived Neural Stem Cells Identifies Human Astrocyte Markers and Signaling Pathways and Transcription Factors Active in Human Astrocytes

PLoS ONE ◽

10.1371/journal.pone.0096139 ◽

2014 ◽

Vol 9 (5) ◽

pp. e96139 ◽

Cited By ~ 22

Author(s):

Nasir Malik ◽

Xiantao Wang ◽

Sonia Shah ◽

Anastasia G. Efthymiou ◽

Bin Yan ◽

...

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Stem Cell ◽

Transcription Factors ◽

Neural Stem Cells ◽

Signaling Pathways ◽

Pluripotent Stem Cell ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Human Astrocytes

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Assembling defenses against therapy-resistant leukemic stem cells: Bcl6 joins the ranks

Journal of Experimental Medicine ◽

10.1084/jem.20112087 ◽

2011 ◽

Vol 208 (11) ◽

pp. 2155-2158 ◽

Cited By ~ 17

Author(s):

Francesca Pellicano ◽

Tessa L. Holyoake

Keyword(s):

Stem Cells ◽

Signaling Pathways ◽

Kinase Inhibitors ◽

Philadelphia Chromosome ◽

B Cell Lymphoma ◽

Leukemic Stem Cells ◽

Cooperative Activity ◽

Foxo Transcription Factors ◽

Complex Signaling ◽

Multiple Signaling

The resistance of leukemic stem cells in response to targeted therapies such as tyrosine kinase inhibitors (TKIs) relies on the cooperative activity of multiple signaling pathways and molecules, including TGFβ, AKT, and FOXO transcription factors (TFs). B cell lymphoma 6 (BCL6) is a transcriptional repressor whose translocation or mutation is associated with diffuse large BCL. New data now show that BCL6 is critical for the maintenance of leukemias driven by the BCR-ABL translocation (Philadelphia chromosome), suggesting that BCL6 is a novel, targetable member of the complex signaling pathways critical for leukemic stem cell survival.

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