Identifying Centriole-associated Factors That Induce Differentiation

Authors

  • Jaba Tkemaladze Author

DOI:

https://doi.org/10.65649/kxemyq77

Keywords:

Centriole, Differentiation, Cell Fate, Asymmetric Division, Signal Transduction, Centrosome, Proteomics

Abstract

The centrosome is fundamentally recognized for its role in cell division and ciliogenesis. However, emerging evidence suggests a non-canonical function: the centriole, particularly the mother centriole, acts as a regulatory hub for cellular differentiation. This article synthesizes data from 65 studies (2010–2024) to test the hypothesis that centrioles are associated with unique sets of regulatory molecules which, upon specific cues, can act as local inducers of cell fate. We systematically identify and classify such Centriole-Associated Fate Determinants (CAFDs), including transcription factors (STAT3, YAP/TAZ, Gli), RNA regulators (Prospero mRNA), kinases (PLK4), and ubiquitin ligase components. We delineate four core mechanistic paradigms governing their function: Asymmetric Segregation, Controlled Release, Local Translation, and Local Degradation. A comparative analysis across neurogenesis, gliogenesis, myogenesis, and mesenchymal differentiation reveals both conserved principles and lineage-specific adaptations of these mechanisms. We further review critical methodological approaches—from centrosomal proteomics to proximity ligation (BioID/APEX) and mRNA-trapping—essential for discovering CAFDs. Finally, we propose an integrative "Centriolar Decision-Making Conveyor" model, positioning this organelle as an active processing station that integrates signals and dispatches instructive cues to the nucleus. This refines our understanding of cell fate specification and highlights the therapeutic potential of manipulating centriolar signaling to direct differentiation in regenerative medicine and oncology.

References

Andersen, J. S., Wilkinson, C. J., Mayor, T., Mortensen, P., Nigg, E. A., & Mann, M. (2003). Proteomic characterization of the human centrosome by protein correlation profiling. Nature, 426(6966), 570–574. DOI: https://doi.org/10.1038/nature02166

Arquint, C., & Nigg, E. A. (2016). The PLK4–STIL–SAS-6 module at the core of centriole duplication. Biochemical Society Transactions, 44(5), 1253–1263. DOI: https://doi.org/10.1042/BST20160116

Bangs, F., & Anderson, K. V. (2017). Primary cilia and mammalian Hedgehog signaling. Cold Spring Harbor Perspectives in Biology, 9(5), a028175. DOI: https://doi.org/10.1101/cshperspect.a028175

Barenz, F., Mayilo, D., & Gruss, O. J. (2011). Centriolar satellites: busy orbits around the centrosome. European Journal of Cell Biology, 90(12), 983–989. DOI: https://doi.org/10.1016/j.ejcb.2011.07.007

Betschinger, J., & Knoblich, J. A. (2004). Dare to be different: asymmetric cell division in Drosophila, C. elegans and vertebrates. Current Biology, 14(16), R674–R685. DOI: https://doi.org/10.1016/j.cub.2004.08.017

Dai, X., Liu, H., Shen, S., Guo, X., Yan, H., Ji, X., ... & Li, S. (2021). YAP activates the Hippo pathway in regulating osteogenesis of mesenchymal stem cells under tension. International Journal of Oral Science, 13(1), 3.

Fong, K. W., Hau, S. Y., Kho, Y. S., Jia, Y., He, L., & Qi, R. Z. (2016). Interaction of CDK5RAP2 with EB1 to track growing microtubule tips and to regulate microtubule dynamics. Molecular Biology of the Cell, 27(22), 3580–3593.

Gilden, J. K., Peck, S., Chen, Y. C. M., & Krummel, M. F. (2012). The septin cytoskeleton facilitates membrane retraction during motility and phagocytosis. Journal of Cell Biology, 196(1), 103–114. DOI: https://doi.org/10.1083/jcb.201105127

Gönczy, P. (2012). Towards a molecular architecture of centriole assembly. Nature Reviews Molecular Cell Biology, 13(7), 425–435. DOI: https://doi.org/10.1038/nrm3373

Holland, A. J., Lan, W., Niessen, S., Hoover, H., & Cleveland, D. W. (2010). Polo-like kinase 4 kinase activity limits centrosome overduplication by autoregulating its own stability. The Journal of Cell Biology, 188(2), 191–198. DOI: https://doi.org/10.1083/jcb.200911102

Hung, V., Udeshi, N. D., Lam, S. S., Loh, K. H., Cox, K. J., Pedram, K., ... & Ting, A. Y. (2016). Spatially resolved proteomic mapping in living cells with the engineered peroxidase APEX2. Nature Protocols, 11(3), 456–475. DOI: https://doi.org/10.1038/nprot.2016.018

Jaba, T. (2022). Dasatinib and quercetin: short-term simultaneous administration yields senolytic effect in humans. Issues and Developments in Medicine and Medical Research Vol. 2, 22-31. DOI: https://doi.org/10.9734/bpi/idmmr/v2/15155D

Kim, M., Kim, T., Johnson, R. L., & Lim, D. S. (2020). Transcriptional co-repressor function of the Hippo pathway transducers YAP and TAZ. Cell Reports, 11(2), 270–282. DOI: https://doi.org/10.1016/j.celrep.2015.03.015

Liao, E. H., Hung, W., Abrams, B., & Zhen, M. (2011). An SCF-like ubiquitin ligase complex that controls presynaptic differentiation. Nature, 480(7375), 111–117.

Mardin, B. R., & Schiebel, E. (2012). Breaking the ties that bind: new advances in centrosome biology. Journal of Cell Biology, 197(1), 11–18. DOI: https://doi.org/10.1083/jcb.201108006

Mitter, S. K., Rao, H. V., Qi, X., Cai, J., Sugrue, A., Dunn, W. A., ... & Rao, V. (2018). Autophagy in the retina: a potential role in age-related macular degeneration. Retinal Degenerative Diseases, 3–14.

Roux, K. J., Kim, D. I., Raida, M., & Burke, B. (2012). A promiscuous biotin ligase fusion protein identifies proximal and interacting proteins in mammalian cells. The Journal of Cell Biology, 196(6), 801–810. DOI: https://doi.org/10.1083/jcb.201112098

Schneider, L., Clement, C. A., Teilmann, S. C., Pazour, G. J., Hoffmann, E. K., Satir, P., & Christensen, S. T. (2005). PDGFRαα signaling is regulated through the primary cilium in fibroblasts. Current Biology, 15(20), 1861–1866. DOI: https://doi.org/10.1016/j.cub.2005.09.012

Shin, J., Kim, H. C., & Kim, Y. K. (2015). Centrosomal localization of phosphorylated STAT3 is involved in astrocyte differentiation. Experimental & Molecular Medicine, 47(3), e148.

Tanos, B. E., Yang, H. J., Soni, R., Wang, W. J., Macaluso, F. P., Asara, J. M., & Tsou, M. F. (2013). Centriole distal appendages promote membrane docking, leading to cilia initiation. Genes & Development, 27(2), 163–168. DOI: https://doi.org/10.1101/gad.207043.112

Tkemaladze, J. (2023). Reduction, proliferation, and differentiation defects of stem cells over time: a consequence of selective accumulation of old centrioles in the stem cells?. Molecular Biology Reports, 50(3), 2751-2761. DOI : https://pubmed.ncbi.nlm.nih.gov/36583780/ DOI: https://doi.org/10.1007/s11033-022-08203-5

Tkemaladze, J. (2024). Editorial: Molecular mechanism of ageing and therapeutic advances through targeting glycative and oxidative stress. Front Pharmacol. 2024 Mar 6;14:1324446. DOI : 10.3389/fphar.2023.1324446. PMID: 38510429; PMCID: PMC10953819. DOI: https://doi.org/10.3389/fphar.2023.1324446

Tkemaladze, J. (2026). Old Centrioles Make Old Bodies. Annals of Rejuvenation Science, 1(1). DOI : https://doi.org/10.65649/yx9sn772 DOI: https://doi.org/10.65649/yx9sn772

Tkemaladze, J. (2026). Visions of the Future. Longevity Horizon, 2(1). DOI : https://doi.org/10.65649/8be27s21 DOI: https://doi.org/10.65649/8be27s21

Vertii, A., Hehnly, H., & Doxsey, S. (2016). The centrosome, a multitalented renaissance organelle. Cold Spring Harbor Perspectives in Biology, 8(12), a025049. DOI: https://doi.org/10.1101/cshperspect.a025049

Wallingford, J. B., & Mitchell, B. (2011). Strange as it may seem: the many links between Wnt signaling, planar cell polarity, and cilia. Genes & Development, 25(3), 201–213. DOI: https://doi.org/10.1101/gad.2008011

Wang, W. J., & Stearns, T. (2017). Centriole asymmetry determines algal cell geometry. Current Opinion in Plant Biology, 35, 61–66.

Wang, X., Tsai, J. W., Imai, J. H., Lian, W. N., Vallee, R. B., & Shi, S. H. (2009). Asymmetric centrosome inheritance maintains neural progenitors in the neocortex. Nature, 461(7266), 947–955. DOI: https://doi.org/10.1038/nature08435

Xie, T. (2012). Control of germline stem cell self-renewal and differentiation in the Drosophila ovary: concerted actions of niche signals and intrinsic factors. Wiley Interdisciplinary Reviews: Developmental Biology, 2(2), 261–273. DOI: https://doi.org/10.1002/wdev.60

Yeh, C. H., Bellon, M., & Nicot, C. (2018). FBXW7: a critical tumor suppressor of human cancers. Molecular Cancer, 17(1), 115. DOI: https://doi.org/10.1186/s12943-018-0857-2

Downloads

Published

2026-01-30

Issue

Section

Theoretical Frameworks

How to Cite

Tkemaladze, J. (2026). Identifying Centriole-associated Factors That Induce Differentiation. Longevity Horizon, 2(3). DOI : https://doi.org/10.65649/kxemyq77

Most read articles by the same author(s)

<< < 1 2 3 4 5 6 7 > >> 

Similar Articles

1-10 of 40

You may also start an advanced similarity search for this article.