Article ; Online: Toll-like receptors 2 and 4 differentially regulate the self-renewal and differentiation of spinal cord neural precursor cells.
2022 Volume 13, Issue 1, Page(s) 117
Abstract: Background: Toll-like receptors (TLRs) represent critical effectors in the host defense response against various pathogens; however, their known function during development has also highlighted a potential role in cell fate determination and neural ... ...
| Abstract | Background: Toll-like receptors (TLRs) represent critical effectors in the host defense response against various pathogens; however, their known function during development has also highlighted a potential role in cell fate determination and neural differentiation. While glial cells and neural precursor cells (NPCs) of the spinal cord express both TLR2 and TLR4, their influence on self-renewal and cell differentiation remains incompletely described. Methods: TLR2, TLR4 knock-out and the wild type mice were employed for spinal cord tissue analysis and NPCs isolation at early post-natal stage. Sox2, FoxJ1 and Ki67 expression among others served to identify the undifferentiated and proliferative NPCs; GFAP, Olig2 and β-III-tubulin markers served to identify astrocytes, oligodendrocytes and neurons respectively after NPC spontaneous differentiation. Multiple comparisons were analyzed using one-way ANOVA, with appropriate corrections such as Tukey's post hoc tests used for comparisons. Results: We discovered that the deletion of TLR2 or TLR4 significantly reduced the number of Sox2-expressing NPCs in the neonatal mouse spinal cord. While TLR2-knockout NPCs displayed enhanced self-renewal, increased proliferation and apoptosis, and delayed neural differentiation, the absence of TLR4 promoted the neural differentiation of NPCs without affecting proliferation, producing long projecting neurons. TLR4 knock-out NPCs showed significantly higher expression of Neurogenin1, that would be involved in the activation of this neurogenic program by a ligand and microenvironment-independent mechanism. Interestingly, the absence of both TLR2 and TLR4, which induces also a significant reduction in the expression of TLR1, in NPCs impeded oligodendrocyte precursor cell maturation to a similar degree. Conclusions: Our data suggest that Toll-like receptors are needed to maintain Sox2 positive neural progenitors in the spinal cord, however possess distinct regulatory roles in mouse neonatal spinal cord NPCs-while TLR2 and TLR4 play a similar role in oligodendrocytic differentiation, they differentially influence neural differentiation. |
|---|---|
| MeSH term(s) | Animals ; Cell Differentiation ; Mice ; Neural Stem Cells/cytology ; Neurons/cytology ; Spinal Cord/cytology ; Toll-Like Receptor 2/genetics ; Toll-Like Receptor 2/metabolism ; Toll-Like Receptor 4/genetics ; Toll-Like Receptor 4/metabolism |
| Chemical Substances | Tlr2 protein, mouse ; Tlr4 protein, mouse ; Toll-Like Receptor 2 ; Toll-Like Receptor 4 |
| Language | English |
| Publishing date | 2022-03-21 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2548671-8 |
| ISSN | 1757-6512 ; 1757-6512 |
| ISSN (online) | 1757-6512 |
| ISSN | 1757-6512 |
| DOI | 10.1186/s13287-022-02798-z |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
Full text online
More links
Kategorien
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.