Progress in Single-Cell RNA Sequencing Data Analysis and Its Applications in the Study of Tumor Heterogeneity

Main Article Content

Qingsong Cai
College of Life Sciences, Sichuan University, Chengdu, Sichuan, 610000, China

DOI: https://doi.org/10.70267/lshe.20260109

Keywords

application, research progress, single-cell sequencing, tumor heterogeneity

Abstract

Tumors are heterogeneous diseases, and their transition to malignancy is often subtle; however, advanced computational tools can elucidate their development and drug resistance. Single-cell RNA sequencing offers high-resolution insights into cellular and molecular changes, enhancing our understanding of cancer dynamics. This review summarizes the important technological breakthroughs since the birth of single-cell sequencing technology and the recent research results concerning tumor heterogeneity and "precision medicine" through single-cell RNA sequencing. Overall, the future of single-cell RNA sequencing in tumor treatment is undoubtedly promising.

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References

  • [1] Rozenblatt-Rosen, O., Regev, A., Oberdoerffer, P., Nawy, T., Hupalowska, A., Rood, J. E., Ashenberg, O., Cerami, E., Coffey, R. J., Demir, E., et al. The Human Tumor Atlas Network: Charting Tumor Transitions across Space and Time at Single-Cell Resolution. Cell. 2020, 181(2), pp. 236-249. https://doi.org/10.1016/j.cell.2020.03.053.
  • [2] Vitale, I., Shema, E., Loi, S. and Galluzzi, L. Intratumoral heterogeneity in cancer progression and response to immunotherapy. Nature Medicine. 2021, 27(2), pp. 212-224. https://doi.org/10.1038/s41591-021-01233-9.
  • [3] Liu, J., Xu, T., Jin, Y., Huang, B. and Zhang, Y. Progress and Clinical Application of Single-Cell Transcriptional Sequencing Technology in Cancer Research. Frontiers in Oncology. 2021, 10, p. 593085. https://doi.org/10.3389/fonc.2020.593085.
  • [4] Erfanian, N., Derakhshani, A., Nasseri, S., Fereidouni, M., Baradaran, B., Jalili Tabrizi, N., Brunetti, O., Bernardini, R., Silvestris, N. and Safarpour, H. Immunotherapy of cancer in single-cell RNA sequencing era: A precision medicine perspective. Biomedicine & Pharmacotherapy. 2022, 146, p. 112558. https://doi.org/10.1016/j.biopha.2021.112558.
  • [5] Lei, Y., Tang, R., Xu, J., Wang, W., Zhang, B., Liu, J., Yu, X. and Shi, S. Applications of single-cell sequencing in cancer research: progress and perspectives. Journal of Hematology & Oncology. 2021, 14(1), p. 91. https://doi.org/10.1186/s13045-021-01105-2.
  • [6] Amelio, I., Bertolo, R., Bove, P., Buonomo, O. C., Candi, E., Chiocchi, M., Cipriani, C., Di Daniele, N., Ganini, C., Juhl, H., et al. Liquid biopsies and cancer omics. Cell Death Discovery. 2020, 6(1), p. 131. https://doi.org/10.1038/s41420-020-00373-0.
  • [7] Malone, E. R., Oliva, M., Sabatini, P. J. B., Stockley, T. L. and Siu, L. L. Molecular profiling for precision cancer therapies. Genome Medicine. 2020, 12(1), p. 8. https://doi.org/10.1186/s13073-019-0703-1.
  • [8] Bühler, M. M., Martin-Subero, J. I., Pan-Hammarström, Q., Campo, E. and Rosenquist, R. Towards precision medicine in lymphoid malignancies. Journal of Internal Medicine. 2022, 292(2), pp. 221-242. https://doi.org/https://doi.org/10.1111/joim.13423.
  • [9] Ding, J., Sharon, N. and Bar-Joseph, Z. Temporal modelling using single-cell transcriptomics. Nature Reviews Genetics. 2022, 23(6), pp. 355-368. https://doi.org/10.1038/s41576-021-00444-7.
  • [10] Li, P.-H., Kong, X.-Y., He, Y.-Z., Liu, Y., Peng, X., Li, Z.-H., Xu, H., Luo, H. and Park, J. Recent developments in application of single-cell RNA sequencing in the tumour immune microenvironment and cancer therapy. Military Medical Research. 2022, 9(1), p. 52. https://doi.org/10.1186/s40779-022-00414-y.
  • [11] Hong, M., Tao, S., Zhang, L., Diao, L.-T., Huang, X., Huang, S., Xie, S.-J., Xiao, Z.-D. and Zhang, H. RNA sequencing: new technologies and applications in cancer research. Journal of Hematology & Oncology. 2020, 13(1), p. 166. https://doi.org/10.1186/s13045-020-01005-x.
  • [12] Gawad, C., Koh, W. and Quake, S. R. Single-cell genome sequencing: current state of the science. Nature Reviews Genetics. 2016, 17(3), pp. 175-188. https://doi.org/10.1038/nrg.2015.16.
  • [13] Picelli, S. Single-cell RNA-sequencing: The future of genome biology is now. RNA Biology. 2017, 14(5), pp. 637-650. https://doi.org/10.1080/15476286.2016.1201618.
  • [14] Zweifel, P., Felder, S. and Meiers, M. Ageing of population and health care expenditure: a red herring? Health Economics. 1999, 8(6), pp. 485-496. https://doi.org/https://doi.org/10.1002/(SICI)1099-1050(199909)8:6<485::AID-HEC461>3.0.CO;2-4.
  • [15] Potter, S. S. Single-cell RNA sequencing for the study of development, physiology and disease. Nature Reviews Nephrology. 2018, 14(8), pp. 479-492. https://doi.org/10.1038/s41581-018-0021-7.
  • [16] Xin, Y., Kim, J., Ni, M., Wei, Y., Okamoto, H., Lee, J., Adler, C., Cavino, K., Murphy, A. J., Yancopoulos, G. D., et al. Use of the Fluidigm C1 platform for RNA sequencing of single mouse pancreatic islet cells. Proceedings of the National Academy of Sciences. 2016, 113(12), pp. 3293-3298. https://doi.org/10.1073/pnas.1602306113.
  • [17] DeLaughter, D. M. The Use of the Fluidigm C1 for RNA Expression Analyses of Single Cells. Current Protocols in Molecular Biology. 2018, 122(1), p. e55. https://doi.org/https://doi.org/10.1002/cpmb.55.
  • [18] Klein, Allon M., Mazutis, L., Akartuna, I., Tallapragada, N., Veres, A., Li, V., Peshkin, L., Weitz, David A. and Kirschner, Marc W. Droplet Barcoding for Single-Cell Transcriptomics Applied to Embryonic Stem Cells. Cell. 2015, 161(5), pp. 1187-1201. https://doi.org/10.1016/j.cell.2015.04.044.
  • [19] Macosko, Evan Z., Basu, A., Satija, R., Nemesh, J., Shekhar, K., Goldman, M., Tirosh, I., Bialas, Allison R., Kamitaki, N., Martersteck, Emily M., et al. Highly Parallel Genome-wide Expression Profiling of Individual Cells Using Nanoliter Droplets. Cell. 2015, 161(5), pp. 1202-1214. https://doi.org/10.1016/j.cell.2015.05.002.
  • [20] Zheng, G. X. Y., Terry, J. M., Belgrader, P., Ryvkin, P., Bent, Z. W., Wilson, R., Ziraldo, S. B., Wheeler, T. D., McDermott, G. P., Zhu, J., et al. Massively parallel digital transcriptional profiling of single cells. Nature Communications. 2017, 8(1), p. 14049. https://doi.org/10.1038/ncomms14049.
  • [21] Papalexi, E. and Satija, R. Single-cell RNA sequencing to explore immune cell heterogeneity. Nature Reviews Immunology. 2018, 18(1), pp. 35-45. https://doi.org/10.1038/nri.2017.76.
  • [22] Ding, S., Chen, X. and Shen, K. Single-cell RNA sequencing in breast cancer: Understanding tumor heterogeneity and paving roads to individualized therapy. Cancer Communications. 2020, 40(8), pp. 329-344. https://doi.org/https://doi.org/10.1002/cac2.12078.
  • [23] Hochgerner, H., Lönnerberg, P., Hodge, R., Mikes, J., Heskol, A., Hubschle, H., Lin, P., Picelli, S., La Manno, G., Ratz, M., et al. STRT-seq-2i: dual-index 5ʹ single cell and nucleus RNA-seq on an addressable microwell array. Scientific Reports. 2017, 7(1), p. 16327. https://doi.org/10.1038/s41598-017-16546-4.
  • [24] Ramsköld, D., Luo, S., Wang, Y.-C., Li, R., Deng, Q., Faridani, O. R., Daniels, G. A., Khrebtukova, I., Loring, J. F., Laurent, L. C., et al. Full-length mRNA-Seq from single-cell levels of RNA and individual circulating tumor cells. Nature Biotechnology. 2012, 30(8), pp. 777-782. https://doi.org/10.1038/nbt.2282.
  • [25] Fan, H. C., Fu, G. K. and Fodor, S. P. A. Combinatorial labeling of single cells for gene expression cytometry. Science. 2015, 347(6222), p. 1258367. https://doi.org/10.1126/science.1258367.
  • [26] Shum, E. Y., Walczak, E. M., Chang, C. and Christina Fan, H., (2019). Quantitation of mRNA Transcripts and Proteins Using the BD Rhapsody™ Single-Cell Analysis System. In Suzuki, Y. (ed.) Single Molecule and Single Cell Sequencing. Singapore: Springer Singapore, pp. 63-79.
  • [27] Liao, S., Zhou, X., Liu, C., Liu, C., Hao, S., Luo, H., Hou, H., Liu, Q., Zhang, Z., Xiao, L., et al. Stereo-cell: Spatial enhanced-resolution single-cell sequencing with high-density DNA nanoball-patterned arrays. Science, 389(6762), p. eadr0475. https://doi.org/10.1126/science.adr0475.
  • [28] Liu, J., Dang, H. and Wang, X. W. The significance of intertumor and intratumor heterogeneity in liver cancer. Experimental & Molecular Medicine. 2018, 50(1), pp. e416-e416. https://doi.org/10.1038/emm.2017.165.
  • [29] Ruan, H., Wang, Z., Zhai, Y., Xu, Y., Pi, L., Zheng, J., Zhou, Y., Zhang, C., Huang, R., Chen, K., et al. Single-cell transcriptome analysis of diffuse large B cells in cerebrospinal fluid of central nervous system lymphoma. iScience. 2021, 24(9), p. 102972. https://doi.org/10.1016/j.isci.2021.102972.
  • [30] Wang, R., Dang, M., Harada, K., Han, G., Wang, F., Pool Pizzi, M., Zhao, M., Tatlonghari, G., Zhang, S., Hao, D., et al. Single-cell dissection of intratumoral heterogeneity and lineage diversity in metastatic gastric adenocarcinoma. Nature Medicine. 2021, 27(1), pp. 141-151. https://doi.org/10.1038/s41591-020-1125-8.
  • [31] Borcherding, N., Voigt, A. P., Liu, V., Link, B. K., Zhang, W. and Jabbari, A. Single-Cell Profiling of Cutaneous T-Cell Lymphoma Reveals Underlying Heterogeneity Associated with Disease Progression. Clinical Cancer Research. 2019, 25(10), pp. 2996-3005. https://doi.org/10.1158/1078-0432.CCR-18-3309.
  • [32] Davis, R. T., Blake, K., Ma, D., Gabra, M. B. I., Hernandez, G. A., Phung, A. T., Yang, Y., Maurer, D., Lefebvre, A. E. Y. T., Alshetaiwi, H., et al. Transcriptional diversity and bioenergetic shift in human breast cancer metastasis revealed by single-cell RNA sequencing. Nature Cell Biology. 2020, 22(3), pp. 310-320. https://doi.org/10.1038/s41556-020-0477-0.
  • [33] Cao, X., Wang, Y., Zhang, W., Zhong, X., Gunes, E. G., Dang, J., Wang, J., Epstein, A. L., Querfeld, C., Sun, Z., et al. Targeting macrophages for enhancing CD47 blockade–elicited lymphoma clearance and overcoming tumor-induced immunosuppression. Blood. 2022, 139(22), pp. 3290-3302. https://doi.org/10.1182/blood.2021013901.
  • [34] Wu, J., Chen, Z., Wu, W., Qin, J., Zhong, R., Meng, J., Yin, Y., Guo, P. and Fan, S. Single-Cell and Bulk RNA Sequencing Highlights Intra-Tumoral Heterogeneity and Malignant Progression Mechanisms in Prostate Cancer. Journal of Cellular and Molecular Medicine. 2025, 29(16), p. e70806. https://doi.org/https://doi.org/10.1111/jcmm.70806.
  • [35] Sun, H., Shi, C., Fang, G., Guo, Q., Du, Z., Chen, G., Wu, Y., Chen, Z.-S., Hua, J., Zhang, Y., et al. Functional tumor-reactive CD8 + T cells in pancreatic cancer. Journal of Experimental & Clinical Cancer Research. 2025, 44(1), p. 253. https://doi.org/10.1186/s13046-025-03517-1.
  • [36] Zhang, W., Li, Y., Li, C. and Huang, Q. Integrated single-cell and bulk transcriptomic profiling reveals cancer-associated fibroblast heterogeneity in glioblastoma and establishes a clinically actionable prognostic model and preliminary experimental validation. Hereditas. 2025, 162(1), p. 173. https://doi.org/10.1186/s41065-025-00548-8.
  • [37] Han, Y., Zhang, L., Sun, D., Cao, G., Wang, Y., Yue, J., Hu, J., Dong, Z., Li, F., Li, T., et al. Spatiotemporal analyses of the pan-cancer single-cell landscape reveal widespread profibrotic ecotypes associated with tumor immunity. Nature Cancer. 2025, 6(11), pp. 1880-1898. https://doi.org/10.1038/s43018-025-01039-5.
  • [38] Huang, D., Ma, N., Li, X., Gou, Y., Duan, Y., Liu, B., Xia, J., Zhao, X., Wang, X., Li, Q., et al. Advances in single-cell RNA sequencing and its applications in cancer research. Journal of Hematology & Oncology. 2023, 16(1), p. 98. https://doi.org/10.1186/s13045-023-01494-6.

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Published
Feb 4, 2026
Conference Proceedings Volume
Vol. 12 (2026): Proceedings of the 2026 International Conference on Life Sciences and Health Engineering (IC-LSHE 2026)
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Articles
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How to Cite

Cai, Qingsong. “Progress in Single-Cell RNA Sequencing Data Analysis and Its Applications in the Study of Tumor Heterogeneity”. Exploring Science Academic Conference Series, vol. 12, Feb. 2026, pp. 72-78, https://doi.org/10.70267/lshe.20260109.

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