Induction of de novo centriole biogenesis in planarian stem cells
DOI:
https://doi.org/10.5281/zenodo.17283229Keywords:
Centriole, De Novo Biogenesis, Planarian, Neoblast, Regeneration, Ciliogenesis, Basal Body, PLK4, SAS-6Abstract
The centriole is a fundamental organelle templating cilia formation and ensuring genomic stability. While most cells assemble centrioles using a pre-existing mother as a template, the de novo pathway allows for assembly in their absence. However, the physiological role and regulation of de novo biogenesis in vivo remain poorly understood. The planarian Schmidtea mediterranea, with its abundant somatic stem cells (neoblasts) and dependence on a massive ciliated epithelium for locomotion, presents a unique model to address this gap. We demonstrate that quiescent neoblasts are acentriolar, lacking the templates for canonical duplication. Upon tissue injury, neoblasts are activated and initiate a programmed de novo centriole biogenesis pathway. Super-resolution microscopy and transmission electron microscopy reveal the formation of cytoplasmic procentriolar foci and mature centrioles, independent of any parental structure. Crucially, genetic ablation of Sas-6 or pharmacological inhibition of PLK4—interventions that effectively block the canonical pathway—fail to prevent the formation of new centrioles and functional basal bodies in the regenerating ciliated epithelium. This work provides the first in vivo evidence in a whole organism for an induced de novo centriole biogenesis pathway in adult somatic stem cells. We propose this pathway is a key evolutionary adaptation, enabling rapid, large-scale ciliogenesis essential for planarian regeneration, and represents a distinct, genetically regulated program separable from canonical duplication.
References
Al Jord, A., Lemaitre, A. I., Delgehyr, N., Faucourt, M., Spassky, N., & Meunier, A. (2017). Centriole amplification by mother and daughter centrioles differs in multiciliated cells. Nature, 547(7664), 561–564. https://doi.org/10.1038/nature23067
Azimzadeh, J., Wong, M. L., Downhour, D. M., Sánchez Alvarado, A., & Marshall, W. F. (2012). Centrosome loss in the evolution of planarians. Science, 335(6067), 461–463. https://doi.org/10.1126/science.1214457
Bazzi, H., & Anderson, K. V. (2014). Acentriolar mitosis activates a p53-dependent apoptosis pathway in the mouse embryo. Proceedings of the National Academy of Sciences, 111(15), E1491–E1500. https://doi.org/10.1073/pnas.1400568111
Bettencourt-Dias, M., Rodrigues-Martins, A., Carpenter, L., Riparbelli, M., Lehmann, L., Gatt, M. K., Carmo, N., Balloux, F., Callaini, G., & Glover, D. M. (2005). SAK/PLK4 is required for centriole duplication and flagella development. Current Biology, 15(24), 2199–2207. https://doi.org/10.1016/j.cub.2005.11.042
Bornens, M. (2012). The centrosome in cells and organisms. Science, 335(6067), 422–426. https://doi.org/10.1126/science.1209037
Conduit, P. T., Wainman, A., & Raff, J. W. (2015). Centrosome function and assembly in animal cells. Nature Reviews Molecular Cell Biology, 16(10), 611–624. https://doi.org/10.1038/nrm4062
Currie, K. W., & Pearson, B. J. (2013). Transcription factors lhx1/5-1 and pitx are required for the maintenance and regeneration of serotonergic neurons in planarians. Development, 140(17), 3577–3588. https://doi.org/10.1242/dev.098590
Fincher, C. T., Wurtzel, O., de Hoog, T., Kravarik, K. M., & Reddien, P. W. (2018). Cell type transcriptome atlas for the planarian Schmidtea mediterranea. Science, 360(6391), eaaq1736. https://doi.org/10.1126/science.aaq1736
Fong, C. S., Mazo, G., Das, T., Goodman, J., Kim, M., O'Rourke, B. P., Izquierdo, D., & Tsou, M. F. (2016). 53BP1 and USP28 mediate p53-dependent cell cycle arrest in response to centrosome loss and prolonged mitosis. eLife, 5, e16270. https://doi.org/10.7554/eLife.16270
Forsthoefel, D. J., James, N. P., Escobar, D. J., Stary, J. M., Vieira, A. P., Waters, F. A., & Newmark, P. A. (2011). An RNAi screen reveals intestinal regulators of branching morphogenesis, differentiation, and stem cell proliferation in planarians. Developmental Cell, 23(4), 691–704. https://doi.org/10.1016/j.devcel.2011.08.008
Fu, J., Hagan, I. M., & Glover, D. M. (2015). The centrosome and its duplication cycle. Cold Spring Harbor Perspectives in Biology, 7(2), a015800. https://doi.org/10.1101/cshperspect.a015800
Gambarotto, D., Zwettler, F. U., Le Guennec, M., Schmidt-Cernohorska, M., Fortun, D., Borgers, S., Heine, J., Schloetel, J. G., Reuss, M., Unser, M., Boyden, E. S., Sauer, M., Hamel, V., & Guichard, P. (2019). Imaging cellular ultrastructures using expansion microscopy (U-ExM). Nature Methods, 16(1), 71–74. https://doi.org/10.1038/s41592-018-0238-1
Godinho, S. A., & Pellman, D. (2014). Causes and consequences of centrosome abnormalities in cancer. Philosophical Transactions of the Royal Society B: Biological Sciences, 369(1650), 20130467. https://doi.org/10.1098/rstb.2013.0467
Gönczy, P. (2012). Towards a molecular architecture of centriole assembly. Nature Reviews Molecular Cell Biology, 13(7), 425–435. https://doi.org/10.1038/nrm3373
Habedanck, R., Stierhof, Y. D., Wilkinson, C. J., & Nigg, E. A. (2005). The Polo kinase Plk4 functions in centriole duplication. Nature Cell Biology, 7(11), 1140–1146. https://doi.org/10.1038/ncb1320
Hayashi, T., Asami, M., Higuchi, S., Shibata, N., & Agata, K. (2006). Isolation of planarian X-ray-sensitive stem cells by fluorescence-activated cell sorting. Development, Growth & Differentiation, 48(6), 371–380. https://doi.org/10.1111/j.1440-169X.2006.00876.x
Hendzel, M. J., Wei, Y., Mancini, M. A., Van Hooser, A., Ranalli, T., Brinkley, B. R., Bazett-Jones, D. P., & Allis, C. D. (1997). Mitosis-specific phosphorylation of histone H3 initiates primarily within pericentromeric heterochromatin during G2 and spreads in an ordered fashion coincident with mitotic chromosome condensation. Chromosoma, 106(6), 348–360. https://doi.org/10.1007/s004120050256
Huang, B., Wang, W., Bates, M., & Zhuang, X. (2008). Three-dimensional super-resolution imaging by stochastic optical reconstruction microscopy. Science, 319(5864), 810–813. https://doi.org/10.1126/science.1153529
Ishikawa, H., & Marshall, W. F. (2011). Ciliogenesis: building the cell's antenna. Nature Reviews Molecular Cell Biology, 12(4), 222–234. https://doi.org/10.1038/nrm3085
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.
Khodjakov, A., Rieder, C. L., Sluder, G., Cassels, G., Sibon, O., & Wang, C. L. (2002). De novo formation of centrosomes in vertebrate cells arrested during S phase. Journal of Cell Biology, 158(7), 1171–1181. https://doi.org/10.1083/jcb.200205102
Kirkham, M., Müller-Reichert, T., O'Connell, K. F., & Gönczy, P. (2019). The centriole duplication cycle. Philosophical Transactions of the Royal Society B: Biological Sciences, 374(1779), 20180386. https://doi.org/10.1098/rstb.2018.0386
Kitagawa, D., Vakonakis, I., Olieric, N., Hilbert, M., Keller, D., Olieric, V., Bortfeld, M., Erat, M. C., Flückiger, I., Gönczy, P., & Steinmetz, M. O. (2011). Structural basis of the 9-fold symmetry of centrioles. Cell, 144(3), 364–375. https://doi.org/10.1016/j.cell.2011.01.008
Kleylein-Sohn, J., Westendorf, J., Le Clech, M., Habedanck, R., Stierhof, Y. D., & Nigg, E. A. (2007). Plk4-induced centriole biogenesis in human cells. Developmental Cell, 13(2), 190–202. https://doi.org/10.1016/j.devcel.2007.07.002
Mitchison, H. M., & Valente, E. M. (2017). Motile and non-motile cilia in human pathology: from function to phenotypes. The Journal of Pathology, 241(2), 294–309. https://doi.org/10.1002/path.4843
Müller-Reichert, T., & Verkade, P. (Eds.). (2012). Correlative Light and Electron Microscopy (Vol. 111). Academic Press.
Newmark, P. A., Reddien, P. W., Cebrià, F., & Sánchez Alvarado, A. (2003). Ingestion of bacterially expressed double-stranded RNA inhibits gene expression in planarians. Proceedings of the National Academy of Sciences, 100(suppl_1), 11861–11865. https://doi.org/10.1073/pnas.1834205100
Nigg, E. A., & Holland, A. J. (2018). Once and only once: mechanisms of centriole duplication and their deregulation in disease. Nature Reviews Molecular Cell Biology, 19(5), 297–312. https://doi.org/10.1038/nrm.2017.127
Petersen, C. P., & Reddien, P. W. (2009). Wnt signaling and the polarity of the primary body axis. Cell, 139(5), 1056–1068. https://doi.org/10.1016/j.cell.2009.11.035
Piperno, G., & Fuller, M. T. (1985). Monoclonal antibodies specific for an acetylated form of α-tubulin recognize the antigen in cilia and flagella from a variety of organisms. The Journal of Cell Biology, 101(6), 2085–2094. https://doi.org/10.1083/jcb.101.6.2085
Plass, M., Solana, J., Wolf, F. A., Ayoub, S., Misios, A., Glazar, P., Obermayer, B., Theis, F. J., Kocks, C., & Rajewsky, N. (2018). Cell type atlas and lineage tree of a whole complex animal by single-cell transcriptomics. Science, 360(6391), eaaq1723. https://doi.org/10.1126/science.aaq1723
Prosser, S. L., & Pelletier, L. (2017). Centriole assembly: A new player enters the game. Nature Cell Biology, 19(11), 1288–1290. https://doi.org/10.1038/ncb3637
Reddien, P. W. (2018). The cellular and molecular basis for planarian regeneration. Cell, 175(2), 327–345. https://doi.org/10.1016/j.cell.2018.09.021
Reddien, P. W., Oviedo, N. J., Jennings, J. R., Jenkin, J. C., & Sánchez Alvarado, A. (2005). SMEDWI-2 is a PIWI-like protein that regulates planarian stem cells. Science, 310(5752), 1327–1330. https://doi.org/10.1126/science.1116110
Reiter, J. F., & Leroux, M. R. (2017). Genes and molecular pathways underpinning ciliopathies. Nature Reviews Molecular Cell Biology, 18(9), 533–547. https://doi.org/10.1038/nrm.2017.60
Rink, J. C. (2013). Stem cell systems and regeneration in planaria. Development, Growth & Differentiation, 55(1), 41–51. https://doi.org/10.1111/dgd.12020
Rodrigues-Martins, A., Riparbelli, M., Callaini, G., Glover, D. M., & Bettencourt-Dias, M. (2007). Revisiting the role of the mother centriole in centriole biogenesis. Science, 316(5827), 1046–1050. https://doi.org/10.1126/science.1142950
Rouhana, L., Weiss, J. A., Forsthoefel, D. J., Lee, H., King, R. S., Inoue, T., Shibata, N., Agata, K., & Newmark, P. A. (2013). RNA interference by feeding in vitro-synthesized double-stranded RNA to planarians: methodology and dynamics. Developmental Dynamics, 242(6), 718–730. https://doi.org/10.1002/dvdy.23950
Rust, M. J., Bates, M., & Zhuang, X. (2006). Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy (STORM). Nature Methods, 3(10), 793–796. https://doi.org/10.1038/nmeth929
Satir, P., & Christensen, S. T. (2007). Overview of structure and function of mammalian cilia. Annual Review of Physiology, 69, 377–400. https://doi.org/10.1146/annurev.physiol.69.040705.141236
Sorokin, S. P. (1968). Reconstructions of centriole formation and ciliogenesis in mammalian lungs. Journal of Cell Science, 3(2), 207–230. https://doi.org/10.1242/jcs.3.2.207
Strnad, P., Leidel, S., Vinogradova, T., Euteneuer, U., Khodjakov, A., & Gönczy, P. (2007). Regulated HsSAS-6 levels ensure formation of a single procentriole per centriole during the centrosome duplication cycle. Developmental Cell, 13(2), 203–213. https://doi.org/10.1016/j.devcel.2007.07.004
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.
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.
Tkemaladze, J. (2025). Through In Vitro Gametogenesis—Young Stem Cells. Longevity Horizon, 1(3). doi : https://doi.org/10.5281/zenodo.15847116
Tkemaladze, J., & Gakely, G. (2025). Induction of de novo centriole biogenesis in planarian stem cells. Longevity Horizon, 1(4). doi : https://doi.org/10.5281/zenodo.17283229
Tkemaladze, J. (2025). The Tkemaladze Method maps cell lineage with mutant mitochondrial transfer. Longevity Horizon, 1(4). doi : https://doi.org/10.5281/zenodo.17236869
Tkemaladze, J. (2025). The Tkemaladze Method: Mapping Cell Lineage with Mutant Mitochondrial Transfer. Preprints. https://doi.org/10.20944/preprints202509.2586.v1
Tkemaladze, J. (2025). Voynich Manuscript Decryption: A Novel Compression-Based Hypothesis and Computational Framework. doi : https://doi.org/10.20944/preprints202509.0403.v1
Tkemaladze, J. (2025). The Centriole Paradox in Planarian Biology: Why Acentriolar Stem Cells Divide and Centriolar Somatic Cells Do Not. doi : https://doi.org/10.20944/preprints202509.0382.v1
Tkemaladze, J., Gakely, G., Gegelia, L., Papadopulo, I., Taktakidze, A., Metreveli, N., ... & Maglakelidze, U. (2025). Production of Functional Gametes from Somatic Cells of the Planarian Schmidtea Mediterranea Via in Vitro Gametogenesis. Longevity Horizon, 1(3). doi : https://doi.org/10.5281/zenodo.17131291
Tkemaladze, J. (2025). The Tkemaladze Method: A Modernized Caucasian Technology for the Production of Shelf-Stable Activated Wheat with Enhanced Nutritional Properties. Longevity Horizon, 1(3). doi : https://doi.org/10.5281/zenodo.16905079
Tkemaladze, J. (2025). Concept to the Living Space. Longevity Horizon, 1(1). doi : https://doi.org/10.5281/zenodo.14635991
Aphkhazava, D., Sulashvili, N., & Tkemaladze, J. (2025). Stem Cell Systems and Regeneration. Georgian Scientists, 7(1), 271–319. doi : https://doi.org/10.52340/gs.2025.07.01.26
Aphkhazava, D., Sulashvili, N., Maglakelidze, G., & Tkemaladze, J. (2025). Ageless Creatures: Molecular Insights into Organisms That Defy Aging. Georgian Scientists, 7(3), 346–396. doi : https://doi.org/10.52340/gs.2025.07.03.24
Chichinadze, K. N., & Tkemaladze, D. V. (2008). Centrosomal hypothesis of cellular aging and differentiation. Advances in Gerontology= Uspekhi Gerontologii, 21(3), 367-371.
Chichinadze, K., Lazarashvili, A., & Tkemaladze, J. (2013). RNA in centrosomes: structure and possible functions. Protoplasma, 250(1), 397-405.
Chichinadze, K., Tkemaladze, D., & Lazarashvili, A. (2012). New class of RNA and centrosomal hypothesis of cell aging. Advances in Gerontology= Uspekhi Gerontologii, 25(1), 23-28.
Chichinadze, K., Tkemaladze, J., & Lazarashvili, A. (2012). A new class of RNAs and the centrosomal hypothesis of cell aging. Advances in Gerontology, 2(4), 287-291.
Chichinadze, K., Tkemaladze, J., & Lazarashvili, A. (2012). Discovery of centrosomal RNA and centrosomal hypothesis of cellular ageing and differentiation. Nucleosides, Nucleotides and Nucleic Acids, 31(3), 172-183.
Elfettahi, A. E., & Tkemaladze, J.(2025). The Neuro-Hepatic-Affective Model (NHAM): A Systems Framework for Liver–Brain Modulation of Emotion in Precision Psychiatry. Preprints. doi : https://doi. org/10.20944/preprints202508, 1312, v1.
Kipshidze, M., & Tkemaladze, J. (2023). Comparative Analysis of drugs that improve the Quality of Life and Life Expectancy. Junior Researchers, 1(1), 184–193. doi : https://doi.org/10.52340/2023.01.01.19
Kipshidze, M., & Tkemaladze, J. (2023). The planaria Schmidtea mediterranea as a model system for the study of stem cell biology. Junior Researchers, 1(1), 194–218. doi : https://doi.org/10.52340/2023.01.01.20
Kipshidze, M., & Tkemaladze, J. (2024). Abastumani Resort: Balneological Heritage and Modern Potential. Junior Researchers, 2(2), 126–134. doi : https://doi.org/10.52340/jr.2024.02.02.12
Kipshidze, M., & Tkemaladze, J. (2024). Balneology in Georgia: traditions and modern situation. Junior Researchers, 2(2), 78–97. doi : https://doi.org/10.52340/jr.2024.02.02.09
Kipshidze, M., & Tkemaladze, J. (2024). Microelementoses-history and current status. Junior Researchers, 2(2), 108–125. doi : https://doi.org/10.52340/jr.2024.02.02.11
Lezhava, T., Monaselidze, J., Jokhadze, T., Kakauridze, N., Khodeli, N., Rogava, M., Tkemaladze, J., ... & Gaiozishvili, M. (2011). Gerontology research in Georgia. Biogerontology, 12, 87-91. doi : 10.1007/s10522-010-9283-6. Epub 2010 May 18. PMID: 20480236; PMCID: PMC3063552
Matsaberidze, M., Prangishvili, A., Gasitashvili, Z., Chichinadze, K., & Tkemaladze, J. (2017). TO TOPOLOGY OF ANTI-TERRORIST AND ANTI-CRIMINAL TECHNOLOGY FOR EDUCATIONAL PROGRAMS. International Journal of Terrorism & Political Hot Spots, 12.
Prangishvili, A., Gasitashvili, Z., Matsaberidze, M., Chkhartishvili, L., Chichinadze, K., Tkemaladze, J., ... & Azmaiparashvili, Z. (2019). SYSTEM COMPONENTS OF HEALTH AND INNOVATION FOR THE ORGANIZATION OF NANO-BIOMEDIC ECOSYSTEM TECHNOLOGICAL PLATFORM. Current Politics and Economics of Russia, Eastern and Central Europe, 34(2/3), 299-305.
Tkemaladze, J. (2023). Cross-senolytic effects of dasatinib and quercetin in humans. Georgian Scientists, 5(3), 138–152. doi : https://doi.org/10.52340/2023.05.03.15
Tkemaladze, J. (2023). Is the selective accumulation of oldest centrioles in stem cells the main cause of organism ageing?. Georgian Scientists, 5(3), 216–235. doi : https://doi.org/10.52340/2023.05.03.22
Tkemaladze, J. (2023). Long-Term Differences between Regenerations of Head and Tail Fragments in Schmidtea Mediterranea Ciw4. Available at SSRN 4257823.
Tkemaladze, J. (2023). Structure and possible functions of centriolar RNA with reference to the centriolar hypothesis of differentiation and replicative senescence. Junior Researchers, 1(1), 156–170. doi : https://doi.org/10.52340/2023.01.01.17
Tkemaladze, J. (2023). The centriolar hypothesis of differentiation and replicative senescence. Junior Researchers, 1(1), 123–141. doi : https://doi.org/10.52340/2023.01.01.15
Tkemaladze, J. (2024). Absence of centrioles and regenerative potential of planaria. Georgian Scientists, 6(4), 59–75. doi : https://doi.org/10.52340/gs.2024.06.04.08
Tkemaladze, J. (2024). Cell center and the problem of accumulation of oldest centrioles in stem cells. Georgian Scientists, 6(2), 304–322. doi : https://doi.org/10.52340/gs.2024.06.02.32
Tkemaladze, J. (2024). Elimination of centrioles. Georgian Scientists, 6(4), 291–307. doi : https://doi.org/10.52340/gs.2024.06.04.25
Tkemaladze, J. (2024). Main causes of intelligence decrease and prospects for treatment. Georgian Scientists, 6(2), 425–432. doi : https://doi.org/10.52340/gs.2024.06.02.44
Tkemaladze, J. (2024). The rate of stem cell division decreases with age. Georgian Scientists, 6(4), 228–242. doi : https://doi.org/10.52340/gs.2024.06.04.21
Tkemaladze, J. (2025). A Universal Approach to Curing All Diseases: From Theoretical Foundations to the Prospects of Applying Modern Biotechnologies in Future Medicine. doi : http://dx.doi.org/10.13140/RG.2.2.24481.11366
Tkemaladze, J. (2025). Adaptive Systems and World Models. doi : http://dx.doi.org/10.13140/RG.2.2.13617.90720
Tkemaladze, J. (2025). Allotransplantation Between Adult Drosophila of Different Ages and Sexes. doi : http://dx.doi.org/10.13140/RG.2.2.27711.62884
Tkemaladze, J. (2025). Anti-Blastomic Substances in the Blood Plasma of Schizophrenia Patients. doi : http://dx.doi.org/10.13140/RG.2.2.12721.08807
Tkemaladze, J. (2025). Centriole Elimination as a Mechanism for Restoring Cellular Order. doi : http://dx.doi.org/10.13140/RG.2.2.12890.66248/1
Tkemaladze, J. (2025). Hypotheses on the Role of Centrioles in Aging Processes. doi : http://dx.doi.org/10.13140/RG.2.2.15014.02887/1
Tkemaladze, J. (2025). Limits of Cellular Division: The Hayflick Phenomenon. doi : http://dx.doi.org/10.13140/RG.2.2.25803.30249
Tkemaladze, J. (2025). Molecular Mechanisms of Aging and Modern Life Extension Strategies: From Antiquity to Mars Colonization. doi : http://dx.doi.org/10.13140/RG.2.2.13208.51204
Tkemaladze, J. (2025). Pathways of Somatic Cell Specialization in Multicellular Organisms. doi : http://dx.doi.org/10.13140/RG.2.2.23348.97929/1
Tkemaladze, J. (2025). Strategic Importance of the Caucasian Bridge and Global Power Rivalries. doi : http://dx.doi.org/10.13140/RG.2.2.19153.03680
Tkemaladze, J. (2025). The Epistemological Reconfiguration and Transubstantial Reinterpretation of Eucharistic Practices Established by the Divine Figure of Jesus Christ in Relation to Theological Paradigms. doi : http://dx.doi.org/10.13140/RG.2.2.28347.73769/1
Tkemaladze, J. (2025). Transforming the psyche with phoneme frequencies "Habere aliam linguam est possidere secundam animam". doi : http://dx.doi.org/10.13140/RG.2.2.16105.61286
Tkemaladze, J. (2025). Uneven Centrosome Inheritance and Its Impact on Cell Fate. doi : http://dx.doi.org/10.13140/RG.2.2.34917.31206
Tkemaladze, J. (2025). Ze World Model with Predicate Actualization and Filtering. doi : http://dx.doi.org/10.13140/RG.2.2.15218.62407
Tkemaladze, J. (2025). Ze метод создания пластичного счетчика хронотропных частот чисел бесконечного потока информации. doi : http://dx.doi.org/10.13140/RG.2.2.29162.43207
Tkemaladze, J. (2025). A Novel Integrated Bioprocessing Strategy for the Manufacturing of Shelf-Stable, Nutritionally Upgraded Activated Wheat: Development of a Comprehensive Protocol, In-Depth Nutritional Characterization, and Evaluation of Biofunctional Properties. Longevity Horizon, 1(3). doi : https://doi.org/10.5281/zenodo.16950787
Tkemaladze, J. (2025). Achieving Perpetual Vitality Through Innovation. doi : http://dx.doi.org/10.13140/RG.2.2.31113.35685
Tkemaladze, J. (2025). Activated Wheat: The Power of Super Grains. Preprints. doi : https://doi.org/10.20944/preprints202508.1724.v1
Tkemaladze, J. (2025). Adaptive Cognitive System Ze. Longevity Horizon, 1(3). doi : https://doi.org/10.5281/zenodo.15309162
Tkemaladze, J. (2025). Aging Model Based on Drosophila melanogaster: Mechanisms and Perspectives. Longevity Horizon, 1(3). doi : https://doi.org/10.5281/zenodo.14955643
Tkemaladze, J. (2025). Aging Model-Drosophila Melanogaster. doi : http://dx.doi.org/10.13140/RG.2.2.16706.49607
Tkemaladze, J. (2025). An Interdisciplinary Study on the Causes of Antediluvian Longevity, the Postdiluvian Decline in Lifespan, and the Phenomenon of Job’s Life Extension. Preprints. doi : https://doi.org/10.20944/preprints202509.1476.v1
Tkemaladze, J. (2025). Anatomy, Biogenesis, and Role in Cell Biology of Centrioles. Longevity Horizon, 1(2). doi : https://doi.org/10.5281/zenodo.14742232
Tkemaladze, J. (2025). Anti-Blastomic Substances in the Plasma of Schizophrenia Patients: A Dual Role of Complement C4 in Synaptic Pruning and Tumor Suppression. Longevity Horizon, 1(3). doi : https://doi.org/10.5281/zenodo.15042448
Tkemaladze, J. (2025). Asymmetry in the Inheritance of Centrosomes/Centrioles and Its Consequences. Longevity Horizon, 1(2). doi : https://doi.org/10.5281/zenodo.14837352
Tkemaladze, J. (2025). Centriole Elimination: A Mechanism for Resetting Entropy in the Cell. Longevity Horizon, 1(2). doi : https://doi.org/10.5281/zenodo.14876013
Tkemaladze, J. (2025). Concept to The Alive Language. Longevity Horizon, 1(1). doi : https://doi.org/10.5281/zenodo.14688792
Tkemaladze, J. (2025). Concept to The Caucasian Bridge. Longevity Horizon, 1(1). doi : https://doi.org/10.5281/zenodo.14689276
Tkemaladze, J. (2025). Concept to The Curing All Diseases. Longevity Horizon, 1(1). doi : https://doi.org/10.5281/zenodo.14676208
Tkemaladze, J. (2025). Concept to The Eternal Youth. Longevity Horizon, 1(1). doi : https://doi.org/10.5281/zenodo.14681902
Tkemaladze, J. (2025). Concept to The Food Security. Longevity Horizon, 1(1). doi : https://doi.org/10.5281/zenodo.14642407
Tkemaladze, J. (2025). Concept to The Restoring Dogmas. Longevity Horizon, 1(1). doi : https://doi.org/10.5281/zenodo.14708980
Tkemaladze, J. (2025). Differentiation of Somatic Cells in Multicellular Organisms. Longevity Horizon, 1(2). doi : https://doi.org/10.5281/10.5281/zenodo.14778927
Tkemaladze, J. (2025). Direct Reprogramming of Somatic Cells to Functional Gametes in Planarians via a Novel In Vitro Gametogenesis Protocol. Preprints. doi : https://doi.org/10.20944/preprints202509.1071.v1
Tkemaladze, J. (2025). Induction of germline-like cells (PGCLCs). Longevity Horizon, 1(3). doi : https://doi.org/10.5281/zenodo.16414775
Tkemaladze, J. (2025). Long-Lived Non-Renewable Structures in the Human Body. doi : http://dx.doi.org/10.13140/RG.2.2.14826.43206
Tkemaladze, J. (2025). Mechanisms of Learning Through the Actualization of Discrepancies. Longevity Horizon, 1(3). doi : https://doi.org/10.5281/zenodo.15200612
Tkemaladze, J. (2025). Memorizing an Infinite Stream of Information in a Limited Memory Space: The Ze Method of a Plastic Counter of Chronotropic Number Frequencies. Longevity Horizon, 1(3). doi : https://doi.org/10.5281/zenodo.15170931
Tkemaladze, J. (2025). Molecular Insights and Radical Longevity from Ancient Elixirs to Mars Colonies. Longevity Horizon, 1(2). doi : https://doi.org/10.5281/zenodo.14895222
Tkemaladze, J. (2025). Ontogenetic Permanence of Non-Renewable Biomechanical Configurations in Homo Sapiens Anatomy. Longevity Horizon, 1(3). doi : https://doi.org/10.5281/zenodo.15086387
Tkemaladze, J. (2025). Protocol for Transplantation of Healthy Cells Between Adult Drosophila of Different Ages and Sexes. Longevity Horizon, 1(2). doi : https://doi.org/10.5281/zenodo.14889948
Tkemaladze, J. (2025). Replicative Hayflick Limit. Longevity Horizon, 1(2). doi : https://doi.org/10.5281/zenodo.14752664
Tkemaladze, J. (2025). Solutions to the Living Space Problem to Overcome the Fear of Resurrection from the Dead. doi : http://dx.doi.org/10.13140/RG.2.2.34655.57768
Tkemaladze, J. (2025). The Centriolar Theory of Differentiation Explains the Biological Meaning of the.
Tkemaladze, J. (2025). The Concept of Data-Driven Automated Governance. Georgian Scientists, 6(4), 399–410. doi : https://doi.org/10.52340/gs.2024.06.04.38
Tkemaladze, J. (2025). The Stage of Differentiation Into Mature Gametes During Gametogenesis in Vitro. Longevity Horizon, 1(3). doi : https://doi.org/10.5281/zenodo.16808827
Tkemaladze, J. (2025). Theory of Lifespan Decline. Longevity Horizon, 1(3). doi : https://doi.org/10.5281/zenodo.17142909
Tkemaladze, J. (2025). Unlocking the Voynich Cipher via the New Algorithmic Coding Hypothesis. Longevity Horizon, 1(3). doi : https://doi.org/10.5281/zenodo.17054312
Tkemaladze, J. (2025). Why do planarian cells without centrioles divide and cells with centrioles do not divide?. Longevity Horizon, 1(3). doi : https://doi.org/10.5281/zenodo.17054142
Tkemaladze, J. (2025). Гаметогенез In Vitro: современное состояние, технологии и перспективы применения. Research Gate. doi : http://dx.doi.org/10.13140/RG.2.2.28647.36000
Tkemaladze, J. Systemic Resilience and Sustainable Nutritional Paradigms in Anthropogenic Ecosystems. doi : http://dx.doi.org/10.13140/RG.2.2.18943.32169/1
Tkemaladze, J. V., & Chichinadze, K. N. (2005). Centriolar mechanisms of differentiation and replicative aging of higher animal cells. Biochemistry (Moscow), 70, 1288-1303.
Tkemaladze, J., & Apkhazava, D. (2019). Dasatinib and quercetin: short-term simultaneous administration improves physical capacity in human. J Biomedical Sci, 8(3), 3.
Tkemaladze, J., & Chichinadze, K. (2005). Potential role of centrioles in determining the morphogenetic status of animal somatic cells. Cell biology international, 29(5), 370-374.
Tkemaladze, J., & Chichinadze, K. (2010). Centriole, differentiation, and senescence. Rejuvenation research, 13(2-3), 339-342.
Tkemaladze, J., & Gakely, G. (2025). A Novel Biotechnological Approach for the Production of Shelf-Stable, Nutritionally Enhanced Activated Wheat: Protocol Development, Nutritional Profiling, and Bioactivity Assessment. doi : https://doi.org/10.20944/preprints202508.1997.v1
Tkemaladze, J., & Samanishvili, T. (2024). Mineral ice cream improves recovery of muscle functions after exercise. Georgian Scientists, 6(2), 36–50. doi : https://doi.org/10.52340/gs.2024.06.02.04
Tkemaladze, J., Tavartkiladze, A., & Chichinadze, K. (2012). Programming and Implementation of Age-Related Changes. In Senescence. IntechOpen.
Tkemaladze, Jaba and Kipshidze, Mariam, Regeneration Potential of the Schmidtea Mediterranea CIW4 Planarian. Available at SSRN: https://ssrn.com/abstract=4633202 or http://dx.doi.org/10.2139/ssrn.4633202
van Breugel, M., Hirono, M., Andreeva, A., Yanagisawa, H. A., Yamaguchi, S., Nakazawa, Y., Morgner, N., Petrovich, M., Ebong, I. O., Robinson, C. V., Johnson, C. M., Veprintsev, D., & Zuber, B. (2011). Structures of SAS-6 suggest its organization in centrioles. Science, 331(6021), 1196–1199. https://doi.org/10.1126/science.1199325
Wenemoser, D., & Reddien, P. W. (2010). Planarian regeneration involves distinct stem cell responses to wounds and tissue absence. Developmental Biology, 344(2), 979–991. https://doi.org/10.1016/j.ydbio.2010.06.017
Winey, M., & O'Toole, E. (2014). Centriole structure. Philosophical Transactions of the Royal Society B: Biological Sciences, 369(1650), 20130457. https://doi.org/10.1098/rstb.2013.0457
Wong, Y. L., Anzola, J. V., Davis, R. L., Yoon, M., Motamedi, A., Kroll, A., Seo, C. P., Hsia, J. E., Kim, S. K., Mitchell, J. W., Mitchell, B. J., Desai, A., Gahman, T. C., Shiau, A. K., & Oegema, K. (2015). Reversible centriole depletion with an inhibitor of Polo-like kinase 4. Science, 348(6239), 1155–1160. https://doi.org/10.1126/science.aaa5111
Wurtzel, O., Cote, L. E., Poirier, A., Satija, R., Regev, A., & Reddien, P. W. (2015). A generic and cell-type-specific wound response precedes regeneration in planarians. Developmental Cell, 35(5), 632–645. https://doi.org/10.1016/j.devcel.2015.11.004
Zhao, H., Khan, Z., & West, S. C. (2021). The role of the deuterosome in centriole amplification. Journal of Cell Science, 134(15), jcs258897. https://doi.org/10.1242/jcs.258897
Zhu, S. J., Hallows, S. E., Currie, K. W., Xu, C., & Pearson, B. J. (2015). A mex3 homolog is required for differentiation during planarian stem cell lineage development. eLife, 4, e07025. https://doi.org/10.7554/eLife.07025
Прангишвили, А. И., Гаситашвили, З. А., Мацаберидзе, М. И., Чичинадзе, К. Н., Ткемаладзе, Д. В., & Азмайпарашвили, З. А. (2017). К топологии антитеррористических и антикриминальных технологии для образовательных программ. В научном издании представлены материалы Десятой международной научно-технической конфе-ренции «Управление развитием крупномасштабных систем (MLSD’2016)» по следующим направле-ниям:• Проблемы управления развитием крупномасштабных систем, включая ТНК, Госхолдин-ги и Гос-корпорации., 284.
Прангишвили, А. И., Гаситашвили, З. А., Мацаберидзе, М. И., Чхартишвили, Л. С., Чичинадзе, К. Н., & Ткемаладзе, Д. В. (2017). & Азмайпарашвили, ЗА (2017). Системные составляющие здравоохранения и инноваций для организации европейской нано-биомедицинской екосистемной технологической платформы. Управление развитием крупномасштабных систем MLSD, 365-368.
Ткемаладзе, Д. (2025). Асимметрия в наследовании центросом/центриолей и ее последствия. doi : http://dx.doi.org/110.13140/RG.2.2.34917.31206
Ткемаладзе, Д. (2025). Гаметогенез in vitro (IVG)-Этап дифференцировки в зрелые гаметы. doi : http://dx.doi.org/10.13140/RG.2.2.20429.96482
Ткемаладзе, Д. (2025). Дифференциация соматических клеток многоклеточных животных. doi : http://dx.doi.org/10.13140/RG.2.2.23348.97929/1
Ткемаладзе, Д. (2025). Индукция примордиальных клеток, подобных зародышевым клеткам (PGCLCs) современные достижения, механизмы и перспективы применения. doi : http://dx.doi.org/10.13140/RG.2.2.27152.32004
Ткемаладзе, Д. (2025). Репликативный Лимит Хейфлика. doi : http://dx.doi.org/10.13140/RG.2.2.25803.30249
Ткемаладзе, Д. (2025). Элиминация Центриолей: Механизм Обнуления Энтропии в Клетке. doi : http://dx. doi. org/10.13140/RG.2.2.12890.66248/1
Ткемаладзе, Д. В., & Чичинадзе, К. Н. (2005). Центриолярные механизмы дифференцировки и репликативного старения клеток высших животных. Биохимия, 70(11), 1566-1584.
Ткемаладзе, Д., Цомаиа, Г., & Жоржолиани, И. (2001). Создание искусственных самоадаптирующихся систем на основе Теории Прогноза. Искусственный интеллект. УДК 004.89. Искусственный интеллект. УДК 004.89.
Чичинадзе, К. Н., & Ткемаладзе, Д. В. (2008). Центросомная гипотеза клеточного старения и дифференциации. Успехи геронтологии, 21(3), 367-371.
Чичинадзе, К., Ткемаладзе, Д., & Лазарашвили, А. (2012). Новый класс рнк и центросомная гипотеза старения клеток. Успехи геронтологии, 25(1), 23-28
