Decoding Stem Cells: Electrophysiological Insights with Functional Analyses

Fatemeh Hosseinpourshirazi; Yusuf Olğar

Decoding Stem Cells: Electrophysiological Insights with Functional Analyses

Abstract

Stem cell research has rapidly advanced in recent years, offering transformative potential for regenerative medicine and disease treatment. However, maximizing their therapeutic efficacy requires precise characterization and identification. By integrating electrophysiological techniques, epigenetic profiling, biochemical approaches, and functional analyses, researchers can gain a deeper understanding of the unique properties of stem cells. This multidisciplinary approach not only enhances their application in regenerative medicine but also paves the way for groundbreaking discoveries in stem cell biology, ultimately driving the development of more effective and targeted therapies.

Keywords

Project Number

None.

References

Abdul, L., Xu, J., Sotra, A., Chaudary, A., Gao, J., Rajasekar, S., Anvari, N., Mahyar, H., and Zhang, B. (2022). D-CryptO: deep learning-based analysis of colon organoid morphology from brightfield images. Lab on a Chip, 22(21), 4118-4128.
Acker, C. D., Yan, P., Pettinato, A., Hinson, T., and Loew, L. M. (2021). Optimization and Validation of Fast Ratiometric Voltage-Sensitive Dye Imaging in Neuronal and Cardiac Tissues and Cultures. Biophysical Journal, 120(3), 331a.
Afouda, B. A. (2022). Towards Understanding the Gene-Specific Roles of GATA Factors in Heart Development: Does GATA4 Lead the Way? International Journal of Molecular Sciences, 23(9), 5255.
Agius, D. R., Kapazoglou, A., Avramidou, E., Baranek, M., Carneros, E., Caro, E., Castiglione, S., Cicatelli, A., Radanovic, A., Ebejer, J.-P., Gackowski, D., Guarino, F., Gulyás, A., Hidvégi, N., Hoenicka, H., Inácio, V., Johannes, F., Karalija, E., Lieberman-Lazarovich, M.,…Vassileva, V. (2023). Exploring the crop epigenome: a comparison of DNA methylation profiling techniques [Review]. Frontiers in Plant Science, 14, 2023.
Albano, M. S., Rothman, W., Scaradavou, A., Blass, D. P., McMannis, J. D., and Rubinstein, P. (2011). Automated Counting of Colony Forming Units (CFU): Towards Standardization of the Measurement of Potency in Cord Blood Cell Therapy Products. Blood, 118(21), 485-485.
Andrews, P. W., and Gokhale, P. J. (2024). A short history of pluripotent stem cells markers. Stem Cell Reports, 19(1), 1-10.
Anjos-Afonso, F., and Bonnet, D. (2023). Human CD34+ hematopoietic stem cell hierarchy: how far are we with its delineation at the most primitive level? Blood, 142(6), 509-518.
Baer, P. C. (2014). Adipose-derived mesenchymal stromal/stem cells: An update on their phenotype in vivo and in vitro. World J Stem Cells, 6(3), 256-265.

Barreto, S., Hamel, L., Schiatti, T., Yang, Y., and George, V. (2019). Cardiac Progenitor Cells from Stem Cells: Learning from Genetics and Biomaterials. Cells, 8(12), 1536.
Barthmes, M., Jose, M. D., Birkner, J. P., Brüggemann, A., Wahl-Schott, C., and Koçer, A. (2014). Studying mechanosensitive ion channels with an automated patch clamp. Eur Biophys J, 43(2-3), 97-104.
Bhartiya, D., Jha, N., Tripathi, A., et al. (2022). Very small embryonic-like stem cells have the potential to win the three-front war on tissue damage, cancer, and aging. Front Cell Dev Biol, 10, 1061022.
Beck, B., and Blanpain, C. (2012). Mechanisms regulating epidermal stem cells. Embo J., 31(9), 2067-2075.
Bean, B. P. (2007). The action potential in mammalian central neurons. Nature Reviews Neuroscience, 8(6), 451-465.
Bell, D. C., and Fermini, B. (2021). Use of automated patch clamp in cardiac safety assessment: past, present and future perspectives. J. Pharmacol Toxicol Methods, 111,107114.
Björk, S., Ojala, E. A., Nordström, T., Ahola, A., Liljeström, M., Hyttinen, J., Kankuri, E., and Mervaala, E. (2017). Evaluation of Optogenetic Electrophysiology Tools in Human Stem Cell-Derived Cardiomyocytes. Front Physiol, 8, 884.
Bongso, A., and Richards, M. (2004). History and perspective of stem cell research. Best Practice & Research Clinical Obstetrics & Gynaecology, 18(6), 827-842.
Bouatta, N., Sorger, P., and AlQuraishi, M. (2021). Protein structure prediction by AlphaFold2: are attention and symmetries all you need? Acta Crystallogr D Struct Biol, 77(Pt 8), 982-991.
Cai, C. L., Liang, X., Shi, Y., Chu, P. H., Pfaff, S. L., Chen, J., and Evans, S. (2003). Isl1 identifies a cardiac progenitor population that proliferates prior to differentiation and contributes a majority of cells to the heart. Dev Cell, 5(6), 877-889.
Campbell, J. G., Miller, D. C., Cundiff, D. D., Feng, Q., and Litofsky, N. S. (2015). Neural stem/progenitor cells react to non-glial cns neoplasms. Springerplus, 4, 53.
Capobianco, S., Chennamaneni, V., Mittal, M., Zhang, N., and Zhang, C. (2010). Endothelial progenitor cells as factors in neovascularization and endothelial repair. World J Cardiol, 2(12), 411-420.
Conde, Inês, Ana Sofia Ribeiro, and Joana Paredes. (2022). Breast cancer stem cell membrane biomarkers: therapy targeting and clinical implications. Cells, 11(6), 934.
Condic, M. L. (2014). Totipotency: what it is and what it is not. Stem Cells Dev, 23(8), 796-812.
Daily, N. J., Du, Z. W., and Wakatsuki, T. (2017). High-Throughput Phenotyping of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes and Neurons Using Electric Field Stimulation and High-Speed Fluorescence Imaging. Assay Drug Dev Technol, 15(4), 178-188.
Dou, W., Zhao, Q., Malhi, M., Liu, X., Zhang, Z., Wang, L., Masse, S., Nanthakumar, K., Hamilton, R., Maynes, J. T., and Sun, Y. (2020). Label-free conduction velocity mapping and gap junction assessment of functional iPSC-Cardiomyocyte monolayers. Biosens Bioelectron, 167, 112468.
Du, Y., Funderburgh, M., Mann, M., et al. (2005). Multipotent Stem Cells in Human Corneal Stroma. Stem cells (Dayton, Ohio), 23, 1266-1275.
Dunlop, J., Bowlby, M., Peri, R., Vasilyev, D., and Arias, R. (2008). High-throughput electrophysiology: an emerging paradigm for ion-channel screening and physiology. Nature Reviews Drug Discovery, 7(4), 358-368.
Dus, M., Ai, M., and Suh, G. S. B. (2013). Taste-independent nutrient selection is mediated by a brain-specific Na+/solute co-transporter in Drosophila. Nature Neuroscience, 16(5), 526-528.
Fisher, M. L., Balinth, S., and Mills, A. A. (2020). p63-related signaling at a glance. J Cell Sci, 133(17).
Foley, J. W., Zhu, S. X., and West, R. B. (2023a). Cost-effective DNA methylation profiling by FML-seq. bioRxiv.
Foley, J. W., Zhu, S. X., and West, R. B. (2023b). Cost-effective DNA methylation profiling by FML-seq. Life Sci Alliance, 6(12).
Friedrich, E. B., Walenta, K., Scharlau, J., Nickenig, G., and Werner, N. (2006). CD34-/CD133+/VEGFR-2+ endothelial progenitor cell subpopulation with potent vasoregenerative capacities. Circ Res, 98(3), e20-25.
Giorgetti, A., Montserrat, N., Aasen, T., Gonzalez, F., Rodríguez-Pizà, I., Vassena, R., Raya, A., Boué, S., Barrero, M. J., Corbella, B. A., Torrabadella, M., Veiga, A., and Izpisua Belmonte, J. C. (2009). Generation of induced pluripotent stem cells from human cord blood using OCT4 and SOX2. Cell Stem Cell, 5(4), 353-357.
Giraldo, E., Palmero-Canton, D., Martinez-Rojas, B., Sanchez-Martin, M. D. M., and Moreno-Manzano, V. (2020). Optogenetic Modulation of Neural Progenitor Cells Improves Neuroregenerative Potential. Int J Mol Sci, 22(1), 365.
Grskovic, M., Javaherian, A., Strulovici, B., & Daley, G. Q. (2011). Induced pluripotent stem cells-opportunities for disease modelling and drug discovery. Nature reviews Drug discovery, 10(12), 915-929.
Gruber, A., Edri, O., Glatstein, S., Goldfracht, I., Huber, I., Arbel, G., Gepstein, A., Chorna, S., and Gepstein, L. (2022). Optogenetic Control of Human Induced Pluripotent Stem Cell-Derived Cardiac Tissue Models. J Am Heart Assoc, 11(4), e021615.
Gutierrez-Aranda, I., Ramos-Mejia, V., Bueno, C., Munoz-Lopez, M., Real, P. J., Mácia, A., Sanchez, L., Ligero, G., Garcia-Parez, J. L., and Menendez, P. (2010). Human induced pluripotent stem cells develop teratoma more efficiently and faster than human embryonic stem cells regardless the site of injection. Stem Cells, 28(9), 1568-1570.
Handgretinger, R., and Kuçi, S. (2013). CD133-Positive Hematopoietic Stem Cells: From Biology to Medicine. Adv Exp Med Biol, 777, 99-111.
Hawkins, R. D., Hon, G. C., Lee, L. K., Ngo, Q., Lister, R., Pelizzola, M., Edsall, L. E., Kuan, S., Luu, Y., Klugman, S., Antosiewicz-Bourget, J., Ye, Z., Espinoza, C., Agarwahl, S., Shen, L., Ruotti, V., Wang, W., Stewart, R., Thomson, J. A.,…Ren, B. (2010). Distinct epigenomic landscapes of pluripotent and lineage-committed human cells. Cell Stem Cell, 6(5), 479-491.
He, X., Wang, Y., Gao, Y., Wang, X., Sun, Z., Zhu, H., Leong, K. W., and Xu, B. (2025). CalciumZero: a toolbox for fluorescence calcium imaging on iPSC derived brain organoids. Brain Informatics, 12(1), 2.
Hellwarth, P. B., Chang, Y., Das, A., Liang, P. Y., Lian, X., Repina, N. A., and Bao, X. (2021). Optogenetic-mediated cardiovascular differentiation and patterning of human pluripotent stem cells. Adv Genet (Hoboken), 2(3), e202100011.
Honda, M., Kiyokawa, J., Tabo, M., and Inoue, T. (2011). Electrophysiological characterization of cardiomyocytes derived from human induced pluripotent stem cells. J Pharmacol Sci, 117(3), 149-159.
Ite, K., Toyoda, M., Akiyama, S., Enosawa, S., Yoshioka, S., Yukitake, T., Yamazaki-Inoue, M., Tatsumi, K., Akutsu, H., Nishina, H., Kimura, T., Otani, N., Nakazawa, A., Fukuda, A., Kasahara, M., and Umezawa, A. (2023). Hypothesis: Colony-forming activity of pluripotent stem cell-derived hepatocyte-like cells for stem cell assay. bioRxiv, 2021.2011.2030.470519.
Jin, X., Jin, X., Jung, J.-E., Beck, S., and Kim, H. (2013). Cell surface Nestin is a biomarker for glioma stem cells. Biochemical and Biophysical Research Communications, 433(4), 496-501.
Kim, H. S., Choi, S. M., Yang, W., Kim, D. S., Lee, D. R., Cho, S. R., and Kim, D. W. (2014). PSA-NCAM(+) neural precursor cells from human embryonic stem cells promote neural tissue integrity and behavioral performance in a rat stroke model. Stem Cell Rev Rep, 10(6), 761-771.
Kimura, H. (2013). Histone modifications for human epigenome analysis. Journal of Human Genetics, 58(7), 439-445.
Korkusuz, P., Köse, S., Yersal, N., and Önen, S. (2019). Magnetic-Based Cell Isolation Technique for the Selection of Stem Cells. Methods Mol Biol, 1879, 153-163.
Lam, D., Enright, H. A., Cadena, J., George, V. K., Soscia, D. A., Tooker, A. C., Triplett, M., Peters, S. K. G., Karande, P., Ladd, A., Bogguri, C., Wheeler, E. K., and Fischer, N. O. (2023). Spatiotemporal analysis of 3D human iPSC-derived neural networks using a 3D multi-electrode array. Frontiers in Cellular Neuroscience, 17, 1287089.
Lauer, M. S. (2014). Personal Reflections on Big Science, Small Science, or the Right Mix. Circulation Research, 114(7), 1080-1082.
Leão, R. N., Reis, A., Emirandetti, A., Lewicka, M., Hermanson, O., and Fisahn, A. (2010). A voltage-sensitive dye-based assay for the identification of differentiated neurons derived from embryonic neural stem cell cultures. PLoS One, 5(11), e13833.
Lee, P., Klos, M., Bollensdorff, C., Hou, L., Ewart, P., Kamp, T. J., Zhang, J., Bizy, A., Guerrero-Serna, G., Kohl, P., Jalife, J., and Herron, T. J. (2012). Simultaneous Voltage and Calcium Mapping of Genetically Purified Human Induced Pluripotent Stem Cell–Derived Cardiac Myocyte Monolayers. Circulation Research, 110(12), 1556-1563.
Lemieux, M. R., Freigassner, B., Hanson, J. L., Thathey, Z., Opp, M. R., Hoeffer, C. A., and Link, C. D. (2024). Multielectrode array characterization of human induced pluripotent stem cell derived neurons in co-culture with primary human astrocytes. PloS one, 19(6), e0303901.
Li, W., and Ding, S. (2010). Small molecules that modulate embryonic stem cell fate and somatic cell reprogramming. Trends Pharmacol Sci, 31(1), 36-45.
Liu, W., Han, J. L., Tomek, J., Bub, G., and Entcheva, E. (2023). Simultaneous Widefield Voltage and Dye-Free Optical Mapping Quantifies Electromechanical Waves in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes. ACS Photonics, 10(4), 1070-1083.
Liu, M., Yue, Y., Chen, X., Xian, K., Dong, C., Shi, M., Xiong, H., Tian, K., Li, Y., Zhang, Q. C., and He, A. (2025). Genome-coverage single-cell histone modifications for embryo lineage tracing. Nature, 640(8059),828-839.
Lopez-Izquierdo, A., Warren, M., Riedel, M., Cho, S., Lai, S., Lux, R. L., Spitzer, K. W., Benjamin, I. J., Tristani-Firouzi, M., and Jou, C. J. (2014). A near-infrared fluorescent voltage-sensitive dye allows for moderate-throughput electrophysiological analyses of human induced pluripotent stem cell-derived cardiomyocytes. Am J Physiol Heart Circ Physiol, 307(9), H1370-1377.
Lu, H. R., Hortigon-Vinagre, M. P., Zamora, V., Kopljar, I., De Bondt, A., Gallacher, D. J., and Smith, G. (2017). Application of optical action potentials in human induced pluripotent stem cells-derived cardiomyocytes to predict drug-induced cardiac arrhythmias. J Pharmacol Toxicol Methods, 87, 53-67. Mahla, R. S. (2016). Stem Cells Applications in Regenerative Medicine and Disease Therapeutics. Int J Cell Biol, 2016, 6940283.
Maleki, M., Ghanbarvand, F., Reza Behvarz, M., Ejtemaei, M., and Ghadirkhomi, E. (2014). Comparison of mesenchymal stem cell markers in multiple human adult stem cells. Int J Stem Cells, 7(2), 118-126.
Ginestier, Christophe, and Max S. Wicha. (2007). Mammary stem cell number as a determinate of breast cancer risk. Breast Cancer Research, 9(4), 109.
Marino, F., Scalise, M., Cianflone, E., Mancuso, T., Aquila, I., Agosti, V., Torella, M., Paolino, D., Mollace, V., Nadal-Ginard, B., and Torella, D. (2019). Role of c-Kit in Myocardial Regeneration and Aging. Front Endocrinol (Lausanne), 10, 371.
Marquardt, T., Ashery-Padan, R., Andrejewski, N., Scardigli, R., Guillemot, F., and Gruss, P. (2001). Pax6 is required for the multipotent state of retinal progenitor cells. Cell, 105(1), 43-55.
Masuda, S., Yokoo, T., Sugimoto, N., Doi, M., Fujishiro, S. H., Takeuchi, K., Kobayashi, E., and Hanazono, Y. (2012). A Simplified In Vitro Teratoma Assay for Pluripotent Stem Cells Injected Into Rodent Fetal Organs. Cell Med, 3(1-3), 103-112.
McDevitt, T. C., and Palecek, S. P. (2008). Innovation in the culture and derivation of pluripotent human stem cells. Curr Opin Biotechnol, 19(5), 527-533.
Mohsen-Kanson, T., Hafner, A. L., Wdziekonski, B., et al. (2013). Expression of cell surface markers during self-renewal and differentiation of human adipose-derived stem cells. Biochem Biophys Res Commun, 430(3), 871-875.
Mildmay-White, A., and Khan, W. (2017). Cell Surface Markers on Adipose-Derived Stem Cells: A Systematic Review. Curr Stem Cell Res Ther, 12(6), 484-492.
Miltenyi, S., Müller, W., Weichel, W., and Radbruch, A. (1990). High gradient magnetic cell separation with MACS. Cytometry, 11(2), 231-238.
Miyawaki, S., Okada, Y., Okano, H., and Miura, K. (2017). Teratoma Formation Assay for Assessing Pluripotency and Tumorigenicity of Pluripotent Stem Cells. Bio-protocol, 7(16), e2518.
Montilla-Rojo, J., Bialecka, M., Wever, K. E., Mummery, C. L., Looijenga, L. H. J., Roelen, B. A. J., and Salvatori, D. C. F. (2023). Teratoma Assay for Testing Pluripotency and Malignancy of Stem Cells: Insufficient Reporting and Uptake of Animal-Free Methods-A Systematic Review. Int J Mol Sci, 24(4).
Morrone, D., Picoi, M. E. L., Felice, F., De Martino, A., Scatena, C., Spontoni, P., Naccarato, A. G., Di Stefano, R., Bortolotti, U., Dal Monte, M., Pini, S., Abelli, M., and Balbarini, A. (2021). Endothelial Progenitor Cells: An Appraisal of Relevant Data from Bench to Bedside. Int J Mol Sci, 22(23), 12874.
Mullen, R. J., Buck, C. R., and Smith, A. M. (1992). NeuN, a neuronal specific nuclear protein in vertebrates. Development, 116(1), 201-211.
Myers, F. B., Zarins, C. K., Abilez, O. J., and Lee, L. P. (2013). Label-free electrophysiological cytometry for stem cell-derived cardiomyocyte clusters. Lab Chip, 13(2), 220-228.
Neher, E., and Sakmann, B. (1992). The patch clamp technique. Scientific American, 266(3), 44-51.
O'Donnell, E. A., Ernst, D. N., and Hingorani, R. (2013). Multiparameter flow cytometry: advances in high resolution analysis. Immune Netw, 13(2), 43-54.
Odorico, J. S., Kaufman, D. S., and Thomson, J. A. (2001). Multilineage differentiation from human embryonic stem cell lines. Stem Cells, 19(3), 193-204.
Ouyang, J. F., Chothani, S., and Rackham, O. J. L. (2023). Deep learning models will shape the future of stem cell research. Stem Cell Reports, 18(1), 6-12.
Mafi., P, Hindocha.,S, Mafi. R,, Griffin., M, and Khan W, S. (2011). Adult mesenchymal stem cells and cell surface characterization - a systematic review of the literature. Open Orthop J, 5(Suppl 2), 253-260.
Paci, M., Penttinen, K., Pekkanen-Mattila, M., and Koivumäki, J. T. (2021). Arrhythmia Mechanisms in Human Induced Pluripotent Stem Cell–Derived Cardiomyocytes. Journal of Cardiovascular Pharmacology, 77(3), 300-316.
Park, S., Koppes, R. A., Froriep, U. P., Jia, X., Achyuta, A. K., McLaughlin, B. L., and Anikeeva, P. (2015). Optogenetic control of nerve growth. Sci Rep, 5, 9669.
Park, T. I.-H., Monzo, H., Mee, E. W., Bergin, P. S., Teoh, H. H., Montgomery, J. M., Faull, R. L. M., Curtis, M. A., and Dragunow, M. (2012). Adult Human Brain Neural Progenitor Cells (NPCs) and Fibroblast-Like Cells Have Similar Properties In Vitro but Only NPCs Differentiate into Neurons. PLoS One, 7(6), e37742.
Park, Y., Franz, C. K., Ryu, H., Luan, H., Cotton, K. Y., Kim, J. U., Chung, T. S., Zhao, S., Vazquez-Guardado, A., Yang, D. S., Li, K., Avila, R., Phillips, J. K., Quezada, M. J., Jang, H., Kwak, S. S., Won, S. M., Kwon, K., Jeong, H.,…Rogers, J. A. (2021). Three-dimensional, multifunctional neural interfaces for cortical spheroids and engineered assembloids. Science Advances, 7(12), eabf9153.
Patel, N., Shen, A., Wada, Y., Blair, M., Mitchell, D., Vanags, L., Woo, S., Ku, M., Dauda, K., Morris, W., Yang, M., Knollmann, B. C., Salem, J. E., Glazer, A. M., and Kroncke, B. M. (2025). A high-performance extracellular field potential analyzer for iPSC-derived cardiomyocytes. Sci Rep, 15(1), 8948.
Poliwoda, S., Noor, N., Downs, E., Schaaf, A., Cantwell, A., Ganti, L., Kaye, A. D., Mosel, L. I., Carroll, C. B., Viswanath, O., and Urits, I. (2022). Stem cells: a comprehensive review of origins and emerging clinical roles in medical practice. Orthop Rev (Pavia), 14(3), 37498.
Ratajczak, M. Z., Zuba-Surma, E., Wojakowski, W., et al. (2014b). Very small embryonic-like stem cells (VSELs) represent a real challenge in stem cell biology: recent pros and cons in the midst of a lively debate. Leukemia, 28(3), 473-484.
Rehman, J. (2010). Empowering self-renewal and differentiation: the role of mitochondria in stem cells. J Mol Med (Berl), 88(10), 981-986.
Robinson, J. P., Ostafe, R., Iyengar, S. N., Rajwa, B., and Fischer, R. (2023). Flow Cytometry: The Next Revolution. Cells, 12(14), 1875.
Rodriguez, Y. B. A., Manso, B. A., and Forsberg, E. C. (2021). CFU-S assay: a historical single-cell assay that offers modern insight into clonal hematopoiesis. Exp Hematol, 104, 1-8.
Roth, F. C., Numberger, M., and Draguhn, A. (2025). The History of the Patch Clamp Technique. In Mastering the Patch Clamp Technique: A Practical Guide (pp. 1-13). Springer.
Ruan, Y., Jiang, S., Musayeva, A., et al. (2021). Corneal Epithelial Stem Cells-Physiology, Pathophysiology and Therapeutic Options. Cells, 10(9), 2302..
Saghatelyan, A. (2023). Calcium signaling as an integrator and decoder of niche factors to control somatic stem cell quiescence and activation. Febs J, 290(3), 677-683.
Samsonraj, R. M., Raghunath, M., Nurcombe, V., Hui, J. H., van Wijnen, A. J., and Cool, S. M. (2017). Concise Review: Multifaceted Characterization of Human Mesenchymal Stem Cells for Use in Regenerative Medicine. Stem Cells Transl Med, 6(12), 2173-2185.
Santos, J. L. S., Araújo, C. A., Rocha, C. A. G., Costa-Ferro, Z. S. M., and Souza, B. S. F. (2023). Modeling Autism Spectrum Disorders with Induced Pluripotent Stem Cell-Derived Brain Organoids. Biomolecules, 13(2).
Sanz Ressel, B. L., Massone, A. R., and Barbeito, C. G. (2021). Expression of the epidermal stem cell marker p63/CK5 in cutaneous papillomas and cutaneous squamous cell carcinomas of dogs. Res Vet Sci, 135, 366-370.
Saraithong, P., Krajcarski, P., Kusaka, Y., Yamada, M., Matsumoto, J., Cunningham, H., Salih, S., Jones, D., Baddhan, D., Hausner, C., Anumonwo, J., Rosenzweig, A., Navarro, M. M., Diaz, L. V., Criscione, J., Kim, D.-H., and Herron, T. J. (2025). AI-guided laser purification of human iPSC-derived cardiomyocytes for next-generation cardiac cell manufacturing. Communications Biology, 8(1), 745.
Sarma, N. J., Takeda, A., and Yaseen, N. R. (2010). Colony forming cell (CFC) assay for human hematopoietic cells. J Vis Exp, 18 (46), 2195.
Schlötzer-Schrehardt, U., and Kruse, F. E. (2005). Identification and characterization of limbal stem cells. Exp Eye Res, 81(3), 247-264.
Seita, J., and Weissman, I. L. (2010). Hematopoietic stem cell: self-renewal versus differentiation. Wiley Interdiscip Rev Syst Biol Med, 2(6), 640-653.
Sheridan, S. D., Surampudi, V., and Rao, R. R. (2012). Analysis of embryoid bodies derived from human induced pluripotent stem cells as a means to assess pluripotency. Stem Cells Int, 2012, 738910.
Shroff, S. N., Das, S. L., Tseng, H.-a., Noueihed, J., Fernandez, F., White, J. A., Chen, C. S., and Han, X. (2020). Voltage Imaging of Cardiac Cells and Tissue Using the Genetically Encoded Voltage Sensor Archon1. iScience, 23(4), 100974.
Smith, K. P., Luong, M. X., and Stein, G. S. (2009). Pluripotency: Toward a gold standard for human ES and iPS cells. Journal of Cellular Physiology, 220(1), 21-29.
Smith, L., Quelch-Cliffe, R., Liu, F., Aguilar, A. H., and Przyborski, S. (2025). Evaluating Strategies to Assess the Differentiation Potential of Human Pluripotent Stem Cells: A Review, Analysis and Call for Innovation. Stem Cell Reviews and Reports, 21(1), 107-125.
Sonoda, Y. (2021). Human CD34-negative hematopoietic stem cells: The current understanding of their biological nature. Experimental Hematology, 96, 13-26.
Spasic, M., Ogayo, E. R., Parsons, A. M., Mittendorf, E. A., van Galen, P., and McAllister, S. S. (2024). Spectral Flow Cytometry Methods and Pipelines for Comprehensive Immunoprofiling of Human Peripheral Blood and Bone Marrow. Cancer Res Commun, 4(3), 895-910.
Stachelscheid, H., Wulf-Goldenberg, A., Eckert, K., Jensen, J., Edsbagge, J., Björquist, P., Rivero, M., Strehl, R., Jozefczuk, J., Prigione, A., Adjaye, J., Urbaniak, T., Bussmann, P., Zeilinger, K., and Gerlach, J. C. (2013). Teratoma formation of human embryonic stem cells in three-dimensional perfusion culture bioreactors. J Tissue Eng Regen Med, 7(9), 729-741.
Steinbeck, J. A., Choi, S. J., Mrejeru, A., Ganat, Y., Deisseroth, K., Sulzer, D., Mosharov, E. V., and Studer, L. (2015). Optogenetics enables functional analysis of human embryonic stem cell-derived grafts in a Parkinson's disease model. Nat Biotechnol, 33(2), 204-209.
Stoppini, L., Heuschkel, M., Loussert-Fonta, C., Baisac, L., and Roux, A. (2024). Versatile micro-electrode array to monitor human iPSC derived 3D neural tissues at air-liquid interface. Frontiers in Cellular Neuroscience, 18. Stuart, T., and Satija, R. (2019). Integrative single-cell analysis. Nature Reviews Genetics, 20(5), 257-272.
Sun, Y.-H., Kao, H. K. J., Chang, C.-W., Merleev, A., Overton, J. L., Pretto, D., Yechikov, S., Maverakis, E., Chiamvimonvat, N., Chan, J. W., and Lieu, D. K. (2020). Human induced pluripotent stem cell line with genetically encoded fluorescent voltage indicator generated via CRISPR for action potential assessment post-cardiogenesis. Stem Cells, 38(1), 90-101.
Suo, Q., Deng, L., Chen, T., Wu, S., Qi, L., Liu, Z., He, T., Tian, H. L., Li, W., Tang, Y., Yang, G. Y., and Zhang, Z. (2023). Optogenetic Activation of Astrocytes Reduces Blood-Brain Barrier Disruption via IL-10 In Stroke. Aging Dis, 14(5), 1870-1886.
Takahashi, K., and Naruse, K. (2015). Planar Patch Clamp System Capable of Recording Mechanosensitive Activity of Ion Channels. Biophysical Journal, 108(2), 584a.
Takahashi, K., and Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126(4), 663-676.
Teoh, P. L., and Saini, N. (2025). Biomarkers, isolation methods, and therapeutic implications of breast cancer stem cells. Cancer Pathogenesis and Therapy, 3(5),392-401.
Thalheim, T., Aust, G., and Galle, J. (2022). Organoid Cultures In Silico: Tools or Toys? Bioengineering (Basel), 10(1), 50.
Theodorakis, N., Feretzakis, G., Tzelves, L., Paxinou, E., Hitas, C., Vamvakou, G., Verykios, V. S., and Nikolaou, M. (2024). Integrating Machine Learning with Multi-Omics Technologies in Geroscience: Towards Personalized Medicine. J Pers Med, 14(9), 931.
Thompson, E. N., Carlino, M. J., Scanlon, V. M., Grimes, H. L., and Krause, D. S. (2023). Assay optimization for the objective quantification of human multilineage colony-forming units. Exp Hematol, 124, 36-44.e33.
Tian, C., Liu, Q., Ma, K., Wang, Y., Chen, Q., Ambroz, R., Klinkebiel, D. L., Li, Y., Huang, Y., Ding, J., Wu, J., and Zheng, J. C. (2013). Characterization of Induced Neural Progenitors from Skin Fibroblasts by a Novel Combination of Defined Factors. Scientific Reports, 3(1), 1345.
Tian, Z., Yu, T., Liu, J., Wang, T., and Higuchi, A. (2023). Chapter One - Introduction to stem cells. In A. Higuchi, Y. Zhou, and S.-H. Chiou (Eds.), Progress in Molecular Biology and Translational Science (Vol. 199, pp. 3-32). Academic Press.
Tønnesen, J., Parish, C. L., Sørensen, A. T., Andersson, A., Lundberg, C., Deisseroth, K., Arenas, E., Lindvall, O., and Kokaia, M. (2011). Functional integration of grafted neural stem cell-derived dopaminergic neurons monitored by optogenetics in an in vitro Parkinson model. PloS one, 6(3), e17560.
Urbich, C., and Dimmeler, S. (2004). Endothelial progenitor cells: characterization and role in vascular biology. Circ Res, 95(4), 343-353.
Vattulainen, M., Ilmarinen, T., Viheriälä, T., et al. (2021). Corneal epithelial differentiation of human pluripotent stem cells generates ABCB5+ and ∆Np63α+ cells with limbal cell characteristics and high wound healing capacity. Stem Cell Research & Therapy, 12(1), 609.
Velier, M., Chateau, A. L., Malenfant, C., Ouffai, S., Calmels, B., Chabannon, C., and Lemarié, C. (2019). Validation of a semi automatic device to standardize quantification of Colony-Forming Unit (CFU) on hematopoietic stem cell products. Cytotherapy, 21(8), 820-823.
Velten, L., Story, B. A., Hernández-Malmierca, P., Raffel, S., Leonce, D. R., Milbank, J., Paulsen, M., Demir, A., Szu-Tu, C., Frömel, R., Lutz, C., Nowak, D., Jann, J.-C., Pabst, C., Boch, T., Hofmann, W.-K., Müller-Tidow, C., Trumpp, A., Haas, S., and Steinmetz, L. M. (2021). Identification of leukemic and pre-leukemic stem cells by clonal tracking from single-cell transcriptomics. Nature Communications, 12(1), 1366.
Willadt, S., Canepari, M., Yan, P., Loew, L. M., and Vogt, K. E. (2014). Combined optogenetics and voltage sensitive dye imaging at single cell resolution. Front Cell Neurosci, 8, 311.
Wilson, N. K., Kent, D. G., Buettner, F., Shehata, M., Macaulay, I. C., Calero-Nieto, F. J., Sánchez Castillo, M., Oedekoven, C. A., Diamanti, E., Schulte, R., Ponting, C. P., Voet, T., Caldas, C., Stingl, J., Green, A. R., Theis, F. J., and Göttgens, B. (2015). Combined Single-Cell Functional and Gene Expression Analysis Resolves Heterogeneity within Stem Cell Populations. Cell Stem Cell, 16(6), 712-724.
Wytock, T. P., and Motter, A. E. (2024). Cell reprogramming design by transfer learning of functional transcriptional networks. Proc Natl Acad Sci U S A, 121(11), e2312942121.
Xu, C., Alameri, A., Leong, W., Johnson, E., Chen, Z., Xu, B., and Leong, K. W. (2024). Multiscale engineering of brain organoids for disease modeling. Advanced Drug Delivery Reviews, 210, 115344.
Xu, J., Lu, C., Jin, S., Meng, Y., Fu, X., Zeng, X., Nussinov, R., and Cheng, F. (2025). Deep learning-based cell-specific gene regulatory networks inferred from single-cell multiome data. Nucleic Acids Research, 53(5), gkaf138.
Xu, R., Wu, C., Tao, Y., Yi, J., Yang, Y., Zhang, X., and Liu, R. (2008). Nestin-positive cells in the spinal cord: a potential source of neural stem cells. International Journal of Developmental Neuroscience, 26(7), 813-820.
Yan, P., Acker, C. D., Biasci, V., Judge, G., Monroe, A., Sacconi, L., and Loew, L. M. (2023). Near-infrared voltage-sensitive dyes based on chromene donor. Proceedings of the National Academy of Sciences, 120(34), e2305093120.
Yang, Q., Hong, Y., Zhao, T., Song, H., and Ming, G. L. (2022). What Makes Organoids Good Models of Human Neurogenesis? Front Neurosci, 16, 872794.
Yang, X., Mann, Koren K., Wu, H., and Ding, J. (2024). scCross: a deep generative model for unifying single-cell multi-omics with seamless integration, cross-modal generation, and in silico exploration. Genome Biology, 25(1), 198.
Yang, Y. (2024). Deciphering Cell Systems: Machine Learning Perspectives And Approaches For The Analysis Of Single-Cell Data. (Ph. D. Thesis), arXiv:2409.19482.
Younes, L., Arrate, F., and Miller, M. I. (2009). Evolutions equations in computational anatomy. Neuroimage, 45(1 Suppl), S40-50.
Yusoff, N. A., Abd Hamid, Z., Budin, S. B., and Taib, I. S. (2025). Hematopoietic stem cell discovery: unveiling the historical and future perspective of colony-forming units assay. PeerJ, 13, e18854.
Zhang, H., and Cohen, A. E. (2017). Optogenetic Approaches to Drug Discovery in Neuroscience and Beyond. Trends Biotechnol, 35(7), 625-639.
Zhang, H., Reichert, E., and Cohen, A. E. (2016). Optical electrophysiology for probing function and pharmacology of voltage-gated ion channels. Elife, 5, e15202.
Zhang, K., Deng, Y., Liu, Y., Luo, J., Glidle, A., Cooper, J. M., Xu, S., Yang, Y., Lv, S., Xu, Z., Wu, Y., Sha, L., Xu, Q., Yin, H., and Cai, X. (2024). Investigating Communication Dynamics in Neuronal Network using 3D Gold Microelectrode Arrays. ACS Nano, 18(26), 17162-17174.
Zhang, P., Nelson, S., Bagby, G. J., Siggins, R., 2nd, Shellito, J. E., and Welsh, D. A. (2008). The lineage-c-Kit+Sca-1+ cell response to Escherichia coli bacteremia in Balb/c mice. Stem Cells, 26(7), 1778-1786.
Zhang, Y., Toyoda, F., Himeno, Y., Noma, A., and Amano, A. (2024). Cell-specific models of hiPSC-CMs developed by the gradient-based parameter optimization method fitting two different action potential waveforms. Scientific Reports, 14(1), 13086.
Zhao, W., Ji, X., Zhang, F., Li, L., and Ma, L. (2012). Embryonic stem cell markers. Molecules, 17(6), 6196-6236.
Zhou, Q. (2013). Induced pluripotent stem cells: current progress and future perspectives. Preface. Genomics Proteomics Bioinformatics, 11(5), 257-258.
Zimmerlin, L., Donnenberg, V. S., Rubin, J. P., and Donnenberg, A. D. (2013). Mesenchymal markers on human adipose stem/progenitor cells. Cytometry A, 83(1), 134-140.
Zuba-Surma, E. K., Wojakowski, W., Ratajczak, M. Z., and Dawn, B. (2011). Very small embryonic-like stem cells: biology and therapeutic potential for heart repair. Antioxid Redox Signal, 15(7), 1821-1834.

Details

Primary Language

English

Subjects

Animal Physiology - Biophysics, Animal Physiology - Systems

Journal Section

Review Article

Authors

Fatemeh Hosseinpourshirazi
0009-0004-1204-5617
Türkiye

Yusuf Olğar ^*
0000-0002-3226-7450
Türkiye

Publication Date

May 27, 2026

Submission Date

November 18, 2025

Acceptance Date

January 23, 2026

Published in Issue

Year 2026 Volume: 3 Number: 1

IZ

https://izlik.org/JA77GG88RT

Cite

RIS / Bibtex

APA

Hosseinpourshirazi, F., & Olğar, Y. (2026). Decoding Stem Cells: Electrophysiological Insights with Functional Analyses. Natural Sciences and Engineering Bulletin, 3(1), 1-18. https://izlik.org/JA77GG88RT

AMA

1.Hosseinpourshirazi F, Olğar Y. Decoding Stem Cells: Electrophysiological Insights with Functional Analyses. NASE. 2026;3(1):1-18. https://izlik.org/JA77GG88RT

Chicago

Hosseinpourshirazi, Fatemeh, and Yusuf Olğar. 2026. “Decoding Stem Cells: Electrophysiological Insights With Functional Analyses”. Natural Sciences and Engineering Bulletin 3 (1): 1-18. https://izlik.org/JA77GG88RT.

EndNote

Hosseinpourshirazi F, Olğar Y (May 1, 2026) Decoding Stem Cells: Electrophysiological Insights with Functional Analyses. Natural Sciences and Engineering Bulletin 3 1 1–18.

IEEE

[1]F. Hosseinpourshirazi and Y. Olğar, “Decoding Stem Cells: Electrophysiological Insights with Functional Analyses”, NASE, vol. 3, no. 1, pp. 1–18, May 2026, [Online]. Available: https://izlik.org/JA77GG88RT

ISNAD

Hosseinpourshirazi, Fatemeh - Olğar, Yusuf. “Decoding Stem Cells: Electrophysiological Insights With Functional Analyses”. Natural Sciences and Engineering Bulletin 3/1 (May 1, 2026): 1-18. https://izlik.org/JA77GG88RT.

JAMA

1.Hosseinpourshirazi F, Olğar Y. Decoding Stem Cells: Electrophysiological Insights with Functional Analyses. NASE. 2026;3:1–18.

MLA

Hosseinpourshirazi, Fatemeh, and Yusuf Olğar. “Decoding Stem Cells: Electrophysiological Insights With Functional Analyses”. Natural Sciences and Engineering Bulletin, vol. 3, no. 1, May 2026, pp. 1-18, https://izlik.org/JA77GG88RT.

Vancouver

1.Fatemeh Hosseinpourshirazi, Yusuf Olğar. Decoding Stem Cells: Electrophysiological Insights with Functional Analyses. NASE [Internet]. 2026 May 1;3(1):1-18. Available from: https://izlik.org/JA77GG88RT