GAGE-seq concurrently profiles multiscale 3D genome organization and gene expression in single cells – Nature Genetics

  • Dekker, J. et al. The 4D nucleome project. Nature 549, 219–226 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cremer, T. & Cremer, C. Chromosome territories, nuclear architecture and gene regulation in mammalian cells. Nat. Rev. Genet. 2, 292–301 (2001).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Rao, S. S. P. et al. A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell 159, 1665–1680 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Xiong, K. & Ma, J. Revealing Hi-C subcompartments by imputing inter-chromosomal chromatin interactions. Nat. Commun. 10, 5069 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dixon, J. R. et al. Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485, 376–380 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nora, E. P. et al. Spatial partitioning of the regulatory landscape of the X-inactivation centre. Nature 485, 381–385 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Phillips-Cremins, J. E. et al. Architectural protein subclasses shape 3D organization of genomes during lineage commitment. Cell 153, 1281–1295 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Beagan, J. A. & Phillips-Cremins, J. E. On the existence and functionality of topologically associating domains. Nat. Genet. 52, 8–16 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Salameh, T. J. et al. A supervised learning framework for chromatin loop detection in genome-wide contact maps. Nat. Commun. 11, 3428 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tang, Z. et al. CTCF-mediated human 3D genome architecture reveals chromatin topology for transcription. Cell 163, 1611–1627 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Marchal, C., Sima, J. & Gilbert, D. M. Control of DNA replication timing in the 3D genome. Nat. Rev. Mol. Cell Biol. 20, 721–737 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ma, J. & Duan, Z. Replication timing becomes intertwined with 3D genome organization. Cell 176, 681–684 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zheng, H. & Xie, W. The role of 3D genome organization in development and cell differentiation. Nat. Rev. Mol. Cell Biol. 20, 535–550 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Misteli, T. The self-organizing genome: principles of genome architecture and function. Cell 183, 28–45 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Spielmann, M., Lupiáñez, D. G. & Mundlos, S. Structural variation in the 3D genome. Nat. Rev. Genet. 19, 453–467 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Oudelaar, A. M. & Higgs, D. R. The relationship between genome structure and function. Nat. Rev. Genet. 22, 154–168 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Nagano, T. et al. Single-cell Hi-C reveals cell-to-cell variability in chromosome structure. Nature 502, 59–64 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zhou, T., Zhang, R. & Ma, J. The 3D genome structure of single cells. Annu. Rev. Biomed. Data Sci. 4, 21–41 (2021).

    Article 
    PubMed 

    Google Scholar
     

  • Stuart, T. & Satija, R. Integrative single-cell analysis. Nat. Rev. Genet. 20, 257–272 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Cao, J. et al. A human cell atlas of fetal gene expression. Science 370, eaba7721 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Calderon, D. et al. The continuum of Drosophila embryonic development at single-cell resolution. Science 377, eabn5800 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ramani, V. et al. Massively multiplex single-cell Hi-C. Nat. Methods 14, 263–266 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nagano, T. et al. Cell-cycle dynamics of chromosomal organization at single-cell resolution. Nature 547, 61–67 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Flyamer, I. M. et al. Single-nucleus Hi-C reveals unique chromatin reorganization at oocyte-to-zygote transition. Nature 544, 110–114 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Stevens, T. J. et al. 3D structures of individual mammalian genomes studied by single-cell Hi-C. Nature 544, 59–64 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tan, L., Xing, D., Chang, C.-H., Li, H. & Xie, X. S. Three-dimensional genome structures of single diploid human cells. Science 361, 924–928 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tan, L. et al. Changes in genome architecture and transcriptional dynamics progress independently of sensory experience during post-natal brain development. Cell 184, 741–758.e17 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Li, G. et al. Joint profiling of DNA methylation and chromatin architecture in single cells. Nat. Methods 16, 991–993 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhang, R., Zhou, T. & Ma, J. Multiscale and integrative single-cell Hi-C analysis with Higashi. Nat. Biotechnol. 40, 254–261 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Luo, C. et al. Single nucleus multi-omics identifies human cortical cell regulatory genome diversity.Cell Genom. 2, 100107 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cardozo Gizzi, A. M. et al. Microscopy-based chromosome conformation capture enables simultaneous visualization of genome organization and transcription in intact organisms. Mol. Cell 74, 212–222.e5 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Mateo, L. J. et al. Visualizing DNA folding and RNA in embryos at single-cell resolution. Nature 568, 49–54 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Su, J.-H., Zheng, P., Kinrot, S. S., Bintu, B. & Zhuang, X. Genome-scale imaging of the 3D organization and transcriptional activity of chromatin. Cell 182, 1641–1659.e26 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Takei, Y. et al. Integrated spatial genomics reveals global architecture of single nuclei. Nature 590, 344–350 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Liu, Z. et al. Linking genome structures to functions by simultaneous single-cell Hi-C and RNA-seq. Science 380, 1070–1076 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ramani, V. et al. Sci-Hi-C: a single-cell Hi-C method for mapping 3D genome organization in large number of single cells. Methods 170, 61–68 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kim, H.-J. et al. Capturing cell type-specific chromatin compartment patterns by applying topic modeling to single-cell Hi-C data. PLoS Comput. Biol. 16, e1008173 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bonora, G. et al. Single-cell landscape of nuclear configuration and gene expression during stem cell differentiation and X inactivation. Genome Biol. 22, 279 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Buenrostro, J. D. et al. Single-cell chromatin accessibility reveals principles of regulatory variation. Nature 523, 486–490 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cusanovich, D. A. et al. Multiplex single cell profiling of chromatin accessibility by combinatorial cellular indexing. Science 348, 910–914 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cao, J. et al. Comprehensive single-cell transcriptional profiling of a multicellular organism. Science 357, 661–667 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rosenberg, A. B. et al. Single-cell profiling of the developing mouse brain and spinal cord with split-pool barcoding. Science 360, 176–182 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ma, S. et al. Chromatin potential identified by shared single-cell profiling of RNA and chromatin. Cell 183, 1103–1116.e20 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lee, D.-S. et al. Simultaneous profiling of 3D genome structure and DNA methylation in single human cells. Nat. Methods 16, 999–1006 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Liu, H. et al. DNA methylation atlas of the mouse brain at single-cell resolution. Nature 598, 120–128 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhang, R., Zhou, T. & Ma, J. Ultrafast and interpretable single-cell 3D genome analysis with Fast-Higashi. Cell Syst. 13, 798–807.e6 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Winick-Ng, W. et al. Cell-type specialization is encoded by specific chromatin topologies. Nature 599, 684–691 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Heffel, M. G. et al. Epigenomic and chromosomal architectural reconfiguration in developing human frontal cortex and hippocampus. Preprint at bioRxiv https://doi.org/10.1101/2022.10.07.511350 (2022).

  • Zhang, M. et al. Spatially resolved cell atlas of the mouse primary motor cortex by MERFISH. Nature 598, 137–143 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chidester, B., Zhou, T., Alam, S. & Ma, J. SPICEMIX enables integrative single-cell spatial modeling of cell identity. Nat. Genet. 55, 78–88 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Law, A. J., Kleinman, J. E., Weinberger, D. R. & Weickert, C. S. Disease-associated intronic variants in the ErbB4 gene are related to altered ErbB4 splice-variant expression in the brain in schizophrenia. Hum. Mol. Genet. 16, 129–141 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zhu, C. et al. Joint profiling of histone modifications and transcriptome in single cells from mouse brain. Nat. Methods 18, 283–292 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhang, Y. et al. Temporal molecular program of human hematopoietic stem and progenitor cells after birth. Dev. Cell 57, 2745–2760.e6 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Nasser, J. et al. Genome-wide enhancer maps link risk variants to disease genes. Nature 593, 238–243 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chen, A. F. et al. NEAT-seq: simultaneous profiling of intra-nuclear proteins, chromatin accessibility and gene expression in single cells. Nat. Methods 19, 547–553 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Plongthongkum, N., Diep, D., Chen, S., Lake, B. B. & Zhang, K. Scalable dual-omics profiling with single-nucleus chromatin accessibility and mRNA expression sequencing 2 (SNARE-seq2). Nat. Protoc. 16, 4992–5029 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Tan, L., Xing, D., Daley, N. & Xie, X. S. Three-dimensional genome structures of single sensory neurons in mouse visual and olfactory systems. Nat. Struct. Mol. Biol. 26, 297–307 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Mulqueen, R. M. et al. High-content single-cell combinatorial indexing. Nat. Biotechnol. 39, 1574–1580 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Collombet, S. et al. Parental-to-embryo switch of chromosome organization in early embryogenesis. Nature 580, 142–146 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Gassler, J. et al. A mechanism of cohesin-dependent loop extrusion organizes zygotic genome architecture. EMBO J. 36, 3600–3618 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cao, J. et al. Joint profiling of chromatin accessibility and gene expression in thousands of single cells. Science 361, 1380–1385 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chen, S., Lake, B. B. & Zhang, K. High-throughput sequencing of the transcriptome and chromatin accessibility in the same cell. Nat. Biotechnol. 37, 1452–1457 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhu, C. et al. An ultra high-throughput method for single-cell joint analysis of open chromatin and transcriptome. Nat. Struct. Mol. Biol. 26, 1063–1070 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mimitou, E. P. et al. Multiplexed detection of proteins, transcriptomes, clonotypes and CRISPR perturbations in single cells. Nat. Methods 16, 409–412 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Xu, W. et al. ISSAAC-seq enables sensitive and flexible multimodal profiling of chromatin accessibility and gene expression in single cells. Nat. Methods 19, 1243–1249 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Xiong, H., Luo, Y., Wang, Q., Yu, X. & He, A. Single-cell joint detection of chromatin occupancy and transcriptome enables higher-dimensional epigenomic reconstructions. Nat. Methods 18, 652–660 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Yao, Z. et al. A taxonomy of transcriptomic cell types across the isocortex and hippocampal formation. Cell 184, 3222–3241.e26 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows–Wheeler transform. Bioinformatics 25, 1754–1760 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15–21 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Goloborodko, A., Abdennur, N. & Venev, S. hbbrandao, gfudenberg. mirnylab/pairtools: v0.3.0. Zenodo https://doi.org/10.5281/zenodo.2649383 (2019).

  • Wolf, F. A., Angerer, P. & Theis, F. J. SCANPY: large-scale single-cell gene expression data analysis. Genome Biol. 19, 15 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhou T. GAGE-seq analysis workflow. Zenodo https://doi.org/10.5281/zenodo.10888453 (2024).