Primary Cilium Is Involved in Stem Cell Differentiation and Renewal through the Regulation of Multiple Signaling Pathways
Abstract
:1. Structure and Function of Primary Cilia
2. Primary Cilia and Signal Transduction
3. Stem Cell Biology and Classification
4. Primary Cilia in Embryonic Development: ECSs
5. Primary Cilia in Organ Development/Maintenance: Adult Stem Cells and iPSCs
6. Role of Primary Cilia in Wnt/β-Catenin Regulation and Stem Cell Biology
7. Role of Primary Cilia in TGF-β Regulation and Stem Cell Biology
8. Role of Primary Cilia in mTOR Regulation and Stem Cell Biology
9. The Role of Autophagy and Primary Cilia in Embryonic Stem Cells
10. Role of Primary Cilia in Notch Regulation and Stem Cell Biology
11. Primary Cilia in Cancer and Cancer Stem Cells
12. Conclusions and Future Perspectives
13. Clinical Relevance
- Understanding how the primary cilium is involved in stem cell biology is crucial to develop new ciliotherapies [25] to eliminate developmental ciliopathy diseases such as Meckel Syndrome.
- Targeting primary cilia and improving its stability/function in patients suffering from bone diseases might be a new approach to improve the patients’ quality of life.
- Deciphering the role of the primary cilium in cancer stem cell biology will likely improve our knowledge and diversify the cancer treatment options as the majority of the signaling pathways are dysregulated in cancers.
14. Outstanding Questions
- Does the knockout or depletion of essential ciliary genes such as IFT88, IFT20, KIF3A (“builders”) have the same impact on differentiation of the embryonic vs. adult stem cells or iPSCs? The answer to this question might allow for defining differences between signaling in dividing vs. quiescent stem cells.
- Since genes such as IFT88 and others have additional non-ciliary functions, the interpretation of KO results might be more complicated than just lack of cilia. Better tools need to be developed and expression controlled to decipher the cilium dependent vs. independent impact of the knockout of IFT and kinesin proteins.
- Would chemical inhibition of these proteins deliver the same results? The answer will allow us to discriminate between activity vs. protein-protein driven functions of the ciliary “builders” or “disassemblers”.
- Would the utilization of proteasome inhibitors in cilia deficient embryos recover the Notch (NICD) levels and HE to HPSC differentiation? The answer will be needed to understand the role of protein biosynthesis/degradation, including autophagy in ciliary homeostasis.
- Can we reprogram cancer stem cells via manipulation of primary cilia dynamics? The answer to this question will require substantial evidence to be gathered on the driving forces of deciliation in cancer, which includes but is not limited to centrosome defects/amplification, lack of cilia, ”builders”, or overexpression of cilia, “disassemblers”.
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Yanardag, S.; Pugacheva, E.N. Primary Cilium Is Involved in Stem Cell Differentiation and Renewal through the Regulation of Multiple Signaling Pathways. Cells 2021, 10, 1428. https://doi.org/10.3390/cells10061428
Yanardag S, Pugacheva EN. Primary Cilium Is Involved in Stem Cell Differentiation and Renewal through the Regulation of Multiple Signaling Pathways. Cells. 2021; 10(6):1428. https://doi.org/10.3390/cells10061428
Chicago/Turabian StyleYanardag, Sila, and Elena N. Pugacheva. 2021. "Primary Cilium Is Involved in Stem Cell Differentiation and Renewal through the Regulation of Multiple Signaling Pathways" Cells 10, no. 6: 1428. https://doi.org/10.3390/cells10061428