Non-canonical Wnt signaling regulates neural stem cell quiescence during homeostasis and after demyelination

Chavali, Manideep; Klingener, Michael; Kokkosis, Alexandros G.; Garkun, Yury; Felong, Sylwia; Maffei, Arianna; Aguirre, Adán

doi:10.1038/s41467-017-02440-0

Cited by 81 publications

(66 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NSC adhesion to the apical niche is maintained through the ncWnt signaling, which in turn regulates Notch signaling activity. Strikingly, as a result of a demyelination injury, tissue homeostasis and repair depends on the downregulation of the ncWnt/Cdc42 axis and activation of canonical Wnt (cWnt)/β-catenin signaling in SVZ NSCs (Chavali et al, 2018 ).…”

Section: Factors Regulating Normal Cell Quiescencementioning

confidence: 99%

Molecular Mechanisms Governing the Stem Cell’s Fate in Brain Cancer: Factors of Stemness and Quiescence

Gulaia

Kumeiko

Shved

et al. 2018

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Cellular quiescence is a reversible, non-cycling state controlled by epigenetic, transcriptional and niche-associated molecular factors. Quiescence is a condition where molecular signaling pathways maintain the poised cell-cycle state whilst enabling rapid cell cycle re-entry. To achieve therapeutic breakthroughs in oncology it is crucial to decipher these molecular mechanisms employed by the cancerous milieu to control, maintain and gear stem cells towards re-activation. Cancer stem-like cells (CSCs) have been extensively studied in most malignancies, including glioma. Here, the aberrant niche activities skew the quiescence/activation equilibrium, leading to rapid tumor relapse after surgery and/or chemotherapy. Unraveling quiescence mechanisms promises to afford prevention of (often multiple) relapses, a key problem in current glioma treatment. This review article covers the current knowledge regarding normal and aberrant cellular quiescence control whilst also exploring how different molecular mechanisms and properties of the neighboring cells can influence the molecular processes behind glioma stem cell quiescence.

show abstract

Section: Factors Regulating Normal Cell Quiescencementioning

confidence: 99%

Molecular Mechanisms Governing the Stem Cell’s Fate in Brain Cancer: Factors of Stemness and Quiescence

Gulaia

Kumeiko

Shved

et al. 2018

Front. Cell. Neurosci.

View full text Add to dashboard Cite

show abstract

“…15,16 However, recent findings have revealed that Ror1 and/or Ror2 are expressed in the tissue stem cells not only during the embryonic development but also in adulthood. [17][18][19][20][21][22] In the adult skeletal muscles, Ror1 is expressed selectively in the adult muscle stem cells, known as satellite cells (SCs), and its expression in SCs can be further enhanced after muscle injury, leading to increased proliferation of SCs, thereby promoting regeneration of the damaged skeletal muscles. 20 In addition, expression of Ror2 is increased in reactive astrocytes that acquire stem cell-like properties in the injured brains, leading to increased proliferation of reactive astrocytes, thereby promoting repair following brain injury.…”

mentioning

confidence: 99%

E2F1‐Ror2 signaling mediates coordinated transcriptional regulation to promote G1/S phase transition in bFGF‐stimulated NIH/3T3 fibroblasts

2020

View full text Add to dashboard Cite

Ror2 signaling has been shown to regulate the cell cycle progression in normal and cancer cells. However, the molecular mechanism of the cell cycle progression upon activation of Ror2 signaling still remains unknown. Here, we found that the expression levels of Ror2 in G1‐arrested NIH/3T3 fibroblasts are low and are rapidly increased following the cell cycle progression induced by basic fibroblast growth factor (bFGF) stimulation. By expressing wild‐type or a dominant negative mutant of E2F1, we show that E2F1 mediates bFGF‐induced expression of Ror2, and that E2F1 binds to the promoter of the Ror2 gene to activate its expression. We also found that G1/S phase transition of bFGF‐stimulated NIH/3T3 cells is delayed by the suppressed expression of Ror2. RNA‐seq analysis revealed that the suppressed expression of Ror2 results in the decreased expression of various E2F target genes concomitantly with increased expression of Forkhead box O (FoxO) target genes, including p21Cip1, and p27Kip1. Moreover, the inhibitory effect of Ror2 knockdown on the cell cycle progression can be restored by suppressed expression of p21Cip1, p27Kip1,or FoxO3a. Collectively, these findings indicate that E2F1‐Ror2 signaling mediates the transcriptional activation and inhibition of E2F1‐driven and FoxO3a‐driven cell cycle‐regulated genes, respectively, thereby promoting G1/S phase transition of bFGF‐stimulated NIH/3T3 cells.

show abstract

“…Wnt signaling has a canonical and a non-canonical branch depending on the downstream involvement of the β-catenin pathway [52]. A shift from the non-canonical to canonical Wnt pathway has been associated with the activation of quiescent NSCs in the lysolecithin model of focal demyelination [53], and β-Catenin signaling is active during remyelination [54]. Indeed, canonical β-catenin dependent [55] and noncanonical β-catenin independent [53] Wnt signaling has been attributed a crucial role in remyelination, although this issue remains controversial [55].…”

Section: Discussionmentioning

confidence: 99%

“…A shift from the non-canonical to canonical Wnt pathway has been associated with the activation of quiescent NSCs in the lysolecithin model of focal demyelination [53], and β-Catenin signaling is active during remyelination [54]. Indeed, canonical β-catenin dependent [55] and noncanonical β-catenin independent [53] Wnt signaling has been attributed a crucial role in remyelination, although this issue remains controversial [55]. Furthermore, active MS plaques express Wnt signaling genes more strongly and accumulate more Wnt protein than chronic lesions and normal appearing white matter [39,56].…”

Section: Discussionmentioning

confidence: 99%

Involvement of Wnt7a in the role of M2c microglia in neural stem cell oligodendrogenesis

Mecha

Yanguas‐Casás

Feliú

et al. 2020

J Neuroinflammation

View full text Add to dashboard Cite

Background: The participation of microglia in CNS development and homeostasis indicate that these cells are pivotal for the regeneration that occurs after demyelination. The clearance of myelin debris and the inflammatorydependent activation of local oligodendrocyte progenitor cells in a demyelinated lesion is dependent on the activation of M2c microglia, which display both phagocytic and healing functions. Emerging interest has been raised about the role of Wnt/β-catenin signaling in oligodendrogenesis and myelination. Besides, cytokines and growth factors released by microglia can control the survival, proliferation, migration, and differentiation of neural stem cells (NSCs), contributing to remyelination through the oligodendrocyte specification of this adult neurogenic niche. Methods: TMEV-IDD model was used to study the contribution of dorsal SVZ stem cells to newly born oligodendrocytes in the corpus callosum following demyelination by (i) en-face dorsal SVZ preparations; (ii) immunohistochemistry; and (iii) cellular tracking. By RT-PCR, we analyzed the expression of Wnt proteins in demyelinated and remyelinating corpus callosum. Using in vitro approaches with microglia cultures and embryonic NSCs, we studied the role of purified myelin, Wnt proteins, and polarized microglia-conditioned medium to NSC proliferation and differentiation. One-way ANOVA followed by Bonferroni's post-hoc test, or a Student's t test were used to establish statistical significance. Results: The demyelination caused by TMEV infection is paralleled by an increase in B1 cells and pinwheels in the dorsal SVZ, resulting in the mobilization of SVZ proliferative progenitors and their differentiation into mature oligodendrocytes. Demyelination decreased the gene expression of Wnt5a and Wnt7a, which was restored during remyelination. In vitro approaches show that Wnt3a enhances NSC proliferation, while Wnt7a and myelin debris promotes oligodendrogenesis from NSCs. As phagocytic M2c microglia secrete Wnt 7a, their conditioned media was found to induce Wnt/β-Catenin signaling in NSCs promoting an oligodendroglial fate. Conclusions: We define here the contribution of microglia to Wnt production depending on their activation state, with M1 microglia secreting the Wnt5a protein and M2c microglia secreting Wnt7a. Collectively, our data reveal the role of reparative microglia in NSC oligodendrogenesis with the involvement of Wnt7a.

show abstract

Non-canonical Wnt signaling regulates neural stem cell quiescence during homeostasis and after demyelination

Cited by 81 publications

References 70 publications

Molecular Mechanisms Governing the Stem Cell’s Fate in Brain Cancer: Factors of Stemness and Quiescence

Molecular Mechanisms Governing the Stem Cell’s Fate in Brain Cancer: Factors of Stemness and Quiescence

E2F1‐Ror2 signaling mediates coordinated transcriptional regulation to promote G1/S phase transition in bFGF‐stimulated NIH/3T3 fibroblasts

Involvement of Wnt7a in the role of M2c microglia in neural stem cell oligodendrogenesis

Contact Info

Product

Resources

About