The DOI matches its Crossref record; 167 of the 167 references it cites were found in a registry or an index.
Single-cell RNA-seq: advances and future challenges
Open accessAbstract
Phenotypically identical cells can dramatically vary with respect to behavior during their lifespan and this variation is reflected in their molecular composition such as the transcriptomic landscape. Single-cell transcriptomics using next-generation transcript sequencing (RNA-seq) is now emerging as a powerful tool to profile cell-to-cell variability on a genomic scale. Its application has already greatly impacted our conceptual understanding of diverse biological processes with broad implications for both basic and clinical research. Different single-cell RNA-seq protocols have been introduced and are reviewed here-each one with its own strengths and current limitations. We further provide an overview of the biological questions single-cell RNA-seq has been used to address, the major findings obtained from such studies, and current challenges and expected future developments in this booming field.
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“new methodologies, such as Hi-C and single-cell sequencing, have yet to be fully integrated at scale with brain genomics data (13–16).”
From Comprehensive functional genomic resource and integrative model for the human brain (2018) · cites this paper as [15]
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“This includes 43,181 proximal and 42,681 distal linkages involving 11,573 protein-encoding target genes (TF–to–target gene via promoter for proximal versus via enhancer–target gene connection for distal) (Fig. 5A) (15, 21).”
From Comprehensive functional genomic resource and integrative model for the human brain (2018) · cites this paper as [15]
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“Using it, we determined which modules were prioritized, as well as the sets of genes associated with latent nodes that were found at each hidden layer (Fig. 8A and table S10) (15, 21).”
From Comprehensive functional genomic resource and integrative model for the human brain (2018) · cites this paper as [15]
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“In addition, current single-cell techniques suffer from low sensitivity and dropouts; thus, it remains challenging to reliably quantify low-abundance transcripts (15, 53).”
From Comprehensive functional genomic resource and integrative model for the human brain (2018) · cites this paper as [15]
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“This is particularly the case for specific brain cell substructures, such as axons and dendrites (15).”
From Comprehensive functional genomic resource and integrative model for the human brain (2018) · cites this paper as [15]
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Cites
RNA-Seq: a revolutionary tool for transcriptomics
Wang, Z., Gerstein, M., & Snyder, M. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2484 · Cited by 13,174
Trapnell, C., Cacchiarelli, D., Grimsby, J., Pokharel, P., Li, S., Morse, M., Lennon, N. J., Livak, K. J., Mikkelsen, T. S., & Rinn, J. L. (2014) · Nature Biotechnology · doi:10.1038/nbt.2859 · Cited by 7,314
Sequencing technologies – the next generation
Metzker, M. L. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2626 · Cited by 7,066
Landscape of transcription in human cells
Djebali, S., Davis, C. A., Merkel, A., Dobin, A., Lassmann, T., Mortazavi, A., Tanzer, A., Lagarde, J., Lin, W., Schlesinger, F., et al. (2012) · Nature · doi:10.1038/nature11233 · Cited by 5,187
Derrien, T., Johnson, R., Bussotti, G., Andrea Tanzer, A., Djebali, S., Tilgner, H., Guernec, G., Martin, D., Merkel, A., Knowles, D. G., et al. (2012) · Genome Research · doi:10.1101/gr.132159.111 · Cited by 5,135
miRBase: annotating high confidence microRNAs using deep sequencing data
Kozomara, A., & Griffiths-Jones, S. (2014) · Nucleic Acids Research · doi:10.1093/nar/gkt1181 · Cited by 5,073
Manipulating the mouse embryo: A laboratory manual
Hogan, B. L. M., Costantini, F. D., & Lacy, E. (1986) · Cited by 4,460
Full-length RNA-seq from single cells using Smart-seq2
Picelli, S., Faridani, O. R., Björklund, Å. K., Winberg, G., Sagasser, S., & Sandberg, R. (2014) · Nature Protocols · doi:10.1038/nprot.2014.006 · Cited by 4,137
Tissue microarrays for high-throughput molecular profiling of tumor specimens
Kononen, J., Bubendorf, L., Kallionimeni, A., Barlund, M. T., Schraml, P., Leighton, S. B., Torhorst, J. K. H., Mihatsch, M. J., Sauter, G., & Kallionimeni, O.-P. (1998) · Nature Medicine · doi:10.1038/nm0798-844 · Cited by 4,101
mRNA-Seq whole-transcriptome analysis of a single cell
Tang, F., Barbacioru, C., Wang, Y., Nordman, E., Lee, C., Xu, N., Wang, X., Bodeau, J., Tuch, B. B., Siddiqui, A., et al. (2009) · Nature Methods · doi:10.1038/nmeth.1315 · Cited by 3,969
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Research works printed but not linked: 4
- 10.1038/nmeth.2639 · DOI · Paper page
- Trapnell C. Cacchiarelli D. Grimsby J. Pokharel P. Li S. Morse M. Lennon N.J. Livak K.J. Mikkelsen T.S. Rinn J.L. The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells. Nat. Biotechnol 2014;32. · DOI · Paper page
- 10.1371/journal.pone.0021208 · DOI
- 10.1038/nature12352 · DOI · Paper page
Cited by
Sorted by citations
Items 801–854 of 854
Tools for Transcriptomics Data Analysis
Tripathy, P. S., Dash, S. S., Rout, A. K., Parida, S. N., Kumar, N., Parhi, J., & Behera, B. K. (2025) · Springer eBooks · doi:10.1007/978-981-95-0285-1_16
Bayesian inference for copy number intra-tumoral heterogeneity from single-cell RNA-sequencing data
Qiao, P., Kwok, C. F., Qian, G., & McCarthy, D. J. (2025) · Biometrics · doi:10.1093/biomtc/ujaf115
KSRV: a Kernel PCA-Based framework for inferring spatial RNA velocity at single-cell resolution
Yan, H., Jiang, J. W., Qiu, H., Shi, Y.-Z., & Zhang, B. (2025) · Frontiers in Genetics · doi:10.3389/fgene.2025.1695803
Farahpour, M., Safarpour, H., Razavi, S. M., & Taghipour‐Gorjikolaie, M. (2025) · Network Modeling Analysis in Health Informatics and Bioinformatics · doi:10.1007/s13721-025-00626-x
Consensus spectral clustering with weighted similarity functions for single-cell RNA sequencing data
Zhu, X., & Fang, Z. (2025) · Communications in Statistics - Simulation and Computation · doi:10.1080/03610918.2025.2578269
Exploiting fluctuations in gene expression to detect causal interactions between genesPreprint
Joly-Smith, E., Talpur, M. M., Allard, P., Papazotos, F., Potvin-Trottier, L., & Hilfinger, A. (2025) · eLife · doi:10.7554/elife.92497.3
Single-cell multi-omics analysis based on nano-LC/MS
Izumi, Y. (2025) · SEIBUTSU BUTSURI KAGAKU · doi:10.2198/electroph.69.17
Fang, C., Selega, A., & Campbell, K. R. (2024) · Figshare · doi:10.6084/m9.figshare.26735316
Gibbs, C. S., Mahmood, O., Bonneau, R., & Cho, K. (2024) · Figshare · doi:10.6084/m9.figshare.26703682
Additional file 4 of scRNASequest: an ecosystem of scRNA-seq analysis, visualization, and publishing
Li, K., Sun, Y. H., Ouyang, Z., Negi, S., Gao, Z., Zhu, J., Wang, W., Chen, Y., Piya, S., Hu, W., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22735497
Lasri, A., Shahrezaei, V., & Sturrock, M. (2022) · Figshare · doi:10.6084/m9.figshare.20098436
Fang, C., Selega, A., & Campbell, K. R. (2024) · Figshare · doi:10.6084/m9.figshare.26735313
Fang, C., Selega, A., & Campbell, K. R. (2024) · Figshare · doi:10.6084/m9.figshare.26735319
Gibbs, C. S., Mahmood, O., Bonneau, R., & Cho, K. (2024) · Figshare · doi:10.6084/m9.figshare.26703688
Klimm, F., Toledo, E. M., Monfeuga, T., Zhang, F., Deane, C. M., & Reinert, G. (2020) · Figshare · doi:10.6084/m9.figshare.13181767
Fang, C., Selega, A., & Campbell, K. R. (2024) · Figshare · doi:10.6084/m9.figshare.26735322
Gibbs, C. S., Mahmood, O., Bonneau, R., & Cho, K. (2024) · Figshare · doi:10.6084/m9.figshare.25566382
Gibbs, C. S., Mahmood, O., Bonneau, R., & Cho, K. (2024) · Figshare · doi:10.6084/m9.figshare.25566268
Gundogdu, P., Loucera, C., Álamo-Álvarez, I., Dopazo, J., & Nepomuceno, I. (2022) · DIGITAL.CSIC (Spanish National Research Council (CSIC)) · doi:10.6084/m9.figshare.17798457
Gibbs, C. S., Mahmood, O., Bonneau, R., & Cho, K. (2024) · Figshare · doi:10.6084/m9.figshare.26703685
Wang, Y., Liu, C., Ji, C., Ma, Z., Liu, Z., Qiao, L., & Zheng, C. (2026) · Current Bioinformatics · doi:10.2174/0115748936401797251030055501
ScCAF: A Cross-Omics Attention Fusion Framework for Single-Cell Multi-Omics Clustering
Yuan, Y., Jin, Y., Wu, L., Wang, P., Li, F., & Ge, D. (2025) · IEEE International Conference on Bioinformatics and Biomedicine (BIBM) · doi:10.1109/bibm66473.2025.11357080
scDVCC:Deep Clustering of scRNA-Seq Based on Dual-View Contrastive Learning
Wang, S., Song, Y., Wu, W., Li, H., Zhang, Y., & Pang, S. (2025) · IEEE International Conference on Bioinformatics and Biomedicine (BIBM) · doi:10.1109/bibm66473.2025.11356414
Discovery and analysis of silencers in Drosophila acting as enhancers in other cellular contexts
Palagi, A. (2018) · theses.fr (ABES) · doi:10.70675/375b5b81z3e0dz42f1z8c46z6f2263bd048b
Le plasmide Ti d’Agrobacterium fabrum C58 : analyse fonctionnelle d’ARN régulateurs
Diel, B. (2017) · theses.fr (ABES) · doi:10.70675/e780ea19zf9e0z4685za1c9zeac189a26b30
Trébulle, P. (2019) · theses.fr (ABES) · doi:10.70675/0e82c666z013bz4790z8f3cz970b82e53b81
Modelling molecular diffusion in the nucleus and its role in gene regulation
de Oliveira, K. A. (2023) · theses.fr (ABES) · doi:10.70675/a447078bz7ad3z42b4zbb21z73194fe1682d
Zhang, M., He, A., Xu, Z. S., Chen, M., Zhang, H., & Mao, W. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1760058
Evolutionary trajectory and development landscape of digital life
ZHANG, B.-W., Jiang, Y., ZHENG, S.-Y., Wang, Z., Lei, M. A., Kai-Yun, M. A. O., Xiong, Y., & Da-Ming, C. H. E. N. (2026) · Shengming kexue · doi:10.3724/cbls.2026034
Xiao, Y., Sun, J., Hao, Y., Xie, L., Duo, H., Zou, Y., Li, Y., Qin, D., Yang, Q., & Li, B. (2026) · TrAC Trends in Analytical Chemistry · doi:10.1016/j.trac.2026.118880
Abdelnaby, M., & Moussa, M. R. (2026) · Journal of Computational Biology · doi:10.1177/15578666261436821
Single-Cell and Spatial Transcriptomics in Renal Injury and Fibrosis Research
Chen, Y., Ye, Z., & Wang, W. (2026) · Kidney Diseases · doi:10.1159/000552224
Hybrid Encoding and Adaptive Guidance for Enhanced Single-Cell Multi-omics Clustering
Li, J., Wang, H., Yu, J., Liang, C., Zhao, X., Zhao, J., & Sun, Y. (2026) · Interdisciplinary Sciences Computational Life Sciences · doi:10.1007/s12539-026-00827-6
Sauda, M. R., Rodrigues, A. B., Lyra, M. L. D. O., Grotto, R. M. T., Gu, L., Melo, T. D. C., & Valente, G. T. (2026) · Molecular Genetics and Genomics · doi:10.1007/s00438-026-02429-9
Wu, J. H., Guo, C., Zhang, L., Cai, G., Liu, Y., & Tang, K. (2026) · Journal of Clinical Laboratory Analysis · doi:10.1002/jcla.70268
Bornet, E., & Westermann, A. J. (2026) · STAR Protocols · doi:10.1016/j.xpro.2026.104651
Self-citationwang, H., Yang, X., Wang, S., Yang, Z., Yang, X., Yang, Y., Li, Z., Ren, Y., Zhang, Q., Zhao, B., et al. (2026) · iMeta · doi:10.1002/imt2.70146
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Porras-Quesada, P. M., Sánchez, P., Morales-Álvarez, C. M., Ramírez‐Mena, A., Álvarez-Cubero, M. J., & Martínez-González, L. J. (2026) · Methods in molecular biology · doi:10.1007/978-1-0716-5050-9_26
Shan, S., Liang, C., & Chen, W. (2026) · Lecture notes in computer science · doi:10.1007/978-981-92-3498-1_40
Duan, Z., He, K., Chen, D., Lin, L., Cao, M., Zhang, S. Y., Zhuang, J., Zhu, Y., Shen, G., & Hu, Y. (2026) · iScience · doi:10.1016/j.isci.2026.116774
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Rehman, S. U., Ali, R., Husien, H. M., & Wang, M. (2026) · DNA and Cell Biology · doi:10.1177/10445498261460199
Wang, Y., Jin, X., Wang, H., Zou, J., Yang, H., & Kong, W. (2026) · Journal of Voice · doi:10.1016/j.jvoice.2026.07.012
Xiang, Y., Peng, J., Shao, Y., Son, J. E., Tagawa, K., Yamada, M., Yamada, S., Yang, Q., & Baiyin, B. (2026) · Horticulturae · doi:10.3390/horticulturae12081045
Meléndez-Flórez, M. P., Rangel, N., Rondón‐Lagos, M., & Ortega‐Recalde, O. (2026) · Biomedicines · doi:10.3390/biomedicines14091902
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Wilkinson, T., & Vogel, J. (2026) · Methods in molecular biology · doi:10.1007/978-1-0716-5368-5_13
Self-citationscI2CL: Effectively fusing single-cell multi-omics by intra- and inter-omics contrastive learning
Liu, W., Peng, H., Li, W., Zhang, Y., Guan, J., & Zhou, S. (2026) · Information Fusion · doi:10.1016/j.inffus.2026.104794
MIGC: Pseudotime differentially expressed genes detection with mutual information
Li, J., & Yuan, Y. (2026) · Quantitative Biology · doi:10.1002/qub2.70057
Artificial Intelligence for Plant Gene Regulatory Networks
Yu, H. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27198819
Johnson, S. W. S., Baker, R. E., & Maini, P. K. (2026) · Theoretical biology · doi:10.1007/978-981-92-0331-4_2
Metadata
- Authors
- Saliba, A.-E., Westermann, A. J., Gorski, S. A., & Vogel, J.
- Affiliations
- University of Würzburg (DE)
- Corresponding author
- Vogel, Jörg
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-07-22
- Volume
- 42
- Issue
- 14
- Pages
- 8845-8860
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC4132710
- OpenAlex
- W2069295116
- Cited by
- 847
- References
- 167
- Citations by year
- 2026: 38 · 2025: 81 · 2024: 92 · 2023: 78 · 2022: 74 · 2021: 69 · 2020: 58 · 2019: 63 · 2018: 67 · 2017: 91 · 2016: 84 · 2015: 46 · 2014: 6
- FWCI
- 7.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nucleic Acids Research (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (acceptedVersion)
- Online Publication Service of Würzburg University (Würzburg University) (submittedVersion, cc-by)
- Funders
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Forschung
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
- Keywords
- single-cell RNA sequencing, single-cell transcriptomics, cell-to-cell variability, transcriptional landscape
- MeSH terms
- Cell Separation, Sequence Analysis, RNA, Gene Expression Profiling, Single-Cell Analysis, High-Throughput Nucleotide Sequencing
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