Regev, A. et al. The human cell atlas. eLife 6, e27041 (2017).
Karlsson, M. et al. A single-cell type transcriptomics map of human tissues. Sci. Adv. 7, eabh2169 (2021).
Consortium, T. T. S. et al. The tabula sapiens: a multiple-organ, single-cell transcriptomic atlas of humans. Science 376, eabl4896 (2022).
Jain, S. et al. Advances and prospects for the Human BioMolecular Atlas Program (HuBMAP). Nat. Cell Biol. 25, 1089–1100 (2023).
Frenkel, M. & Raman, S. Discovering mechanisms of human genetic variation and controlling cell states at scale. Trends Genet. 40, 587–600 (2024).
Rafelski, S. M. & Theriot, J. A. Establishing a conceptual framework for holistic cell states and state transitions. Cell 187, 2633–2651 (2024).
Zhang, M. et al. Molecularly defined and spatially resolved cell atlas of the whole mouse brain. Nature 624, 343–354 (2023).
Patel, A. S. & Yanai, I. A developmental constraint model of cancer cell states and tumor heterogeneity. Cell 187, 2907–2918 (2024).
Rood, J. E., Maartens, A., Hupalowska, A., Teichmann, S. A. & Regev, A. Impact of the Human Cell Atlas on medicine. Nat. Med. 28, 2486–2496 (2022).
Joung, J. et al. A transcription factor atlas of directed differentiation. Cell 186, 209–229.e26 (2023).
Gilbert, L. A. et al. Genome-scale CRISPR-mediated control of gene repression and activation. Cell 159, 647–661 (2014).
Konermann, S. et al. Genome-scale transcriptional activation by an engineered CRISPR–Cas9 complex. Nature 517, 583–588 (2015).
Liu, Y. et al. CRISPR activation screens systematically identify factors that drive neuronal fate and reprogramming. Cell Stem Cell 23, 758–771.e8 (2018).
Norman, T. M. et al. Exploring genetic interaction manifolds constructed from rich single-cell phenotypes. Science 365, 786–793 (2019).
Tian, R. et al. Genome-wide CRISPRi/a screens in human neurons link lysosomal failure to ferroptosis. Nat. Neurosci. 24, 1020–1034 (2021).
Yang, J. et al. Genome-scale CRISPRa screen identifies novel factors for cellular reprogramming. Stem Cell Rep. 12, 757–771 (2019).
Sanson, K. R. et al. Optimized libraries for CRISPR–Cas9 genetic screens with multiple modalities. Nat. Commun. 9, 5416 (2018).
Papalexi, E. et al. Characterizing the molecular regulation of inhibitory immune checkpoints with multimodal single-cell screens. Nat. Genet. 53, 322–331 (2021).
Griffith, A. L. et al. Optimization of Cas12a for multiplexed genome-scale transcriptional activation. Cell Genomics 3, 100387 (2023).
Adamson, B. et al. A multiplexed single-cell CRISPR screening platform enables systematic dissection of the unfolded protein response. Cell 167, 1867–1882.e21 (2016).
Dixit, A. et al. Perturb-seq: dissecting molecular circuits with scalable single-cell RNA profiling of pooled genetic screens. Cell 167, 1853–1866.e17 (2016).
Bock, C. et al. High-content CRISPR screening. Nat. Rev. Methods Prim. 2, 8 (2022).
Pacalin, N. M. et al. Bidirectional epigenetic editing reveals hierarchies in gene regulation. Nat. Biotechnol. 43, 355–368 (2025).
Schmidt, R. et al. CRISPR activation and interference screens decode stimulation responses in primary human T cells. Science 375, eabj4008 (2022).
Chardon, F. M. et al. Multiplex, single-cell CRISPRa screening for cell type specific regulatory elements. Nat. Commun. 15, 8209 (2024).
Replogle, J. M. et al. Mapping information-rich genotype–phenotype landscapes with genome-scale Perturb-seq. Cell 185, 2559–2575.e28 (2022).
Smith, M. H. et al. Drivers of heterogeneity in synovial fibroblasts in rheumatoid arthritis. Nat. Immunol. 24, 1200–1210 (2023).
Wei, K. et al. Notch signalling drives synovial fibroblast identity and arthritis pathology. Nature 582, 259–264 (2020).
Mizoguchi, F. et al. Functionally distinct disease-associated fibroblast subsets in rheumatoid arthritis. Nat. Commun. 9, 789 (2018).
Smillie, C. S. et al. Intra- and Inter-cellular rewiring of the human colon during ulcerative colitis. Cell 178, 714–730.e22 (2019).
Kinchen, J. et al. Structural remodeling of the human colonic mesenchyme in inflammatory bowel disease. Cell 175, 372–386.e17 (2018).
Cadinu, P. et al. Charting the cellular biogeography in colitis reveals fibroblast trajectories and coordinated spatial remodeling. Cell 187, 2010–2028.e30 (2024).
Tsukui, T., Wolters, P. J. & Sheppard, D. Alveolar fibroblast lineage orchestrates lung inflammation and fibrosis. Nature 631, 627–634 (2024).
Tsukui, T. et al. Collagen-producing lung cell atlas identifies multiple subsets with distinct localization and relevance to fibrosis. Nat. Commun. 11, 1920 (2020).
Amrute, J. M. et al. Targeting immune–fibroblast cell communication in heart failure. Nature 635, 423–433 (2024).
Alexanian, M. et al. Chromatin remodelling drives immune cell–fibroblast communication in heart failure. Nature 635, 434–443 (2024).
Chen, X. & Song, E. Turning foes to friends: targeting cancer-associated fibroblasts. Nat. Rev. Drug Discov. 18, 99–115 (2019).
Pradhan, R. N., Krishnamurty, A. T., Fletcher, A. L., Turley, S. J. & Müller, S. A bird’s eye view of fibroblast heterogeneity: a pan-disease, pan-cancer perspective. Immunological Rev. 302, 299–320 (2021).
Buechler, M. B. et al. Cross-tissue organization of the fibroblast lineage. Nature 593, 575–579 (2021).
Korsunsky, I. et al. Cross-tissue, single-cell stromal atlas identifies shared pathological fibroblast phenotypes in four chronic inflammatory diseases. Med 3, 481–518.e14 (2022).
Gao, Y. et al. Cross-tissue human fibroblast atlas reveals myofibroblast subtypes with distinct roles in immune modulation. Cancer Cell 42, 1764–1783.e10 (2024).
Croft, A. P. et al. Distinct fibroblast subsets drive inflammation and damage in arthritis. Nature 570, 246–251 (2019).
Krishnamurty, A. T. et al. LRRC15+ myofibroblasts dictate the stromal setpoint to suppress tumour immunity. Nature 611, 148–154 (2022).
McCartney, E. E., Chung, Y. & Buechler, M. B. Life of Pi: exploring functions of Pi16+ fibroblasts. F1000Res 13, 126 (2024).
Melms, J. C. et al. A molecular single-cell lung atlas of lethal COVID-19. Nature 595, 114–119 (2021).
Horlbeck, M. A. et al. Compact and highly active next-generation libraries for CRISPR-mediated gene repression and activation. eLife 5, e19760 (2016).
Replogle, J. M. et al. Maximizing CRISPRi efficacy and accessibility with dual-sgRNA libraries and optimal effectors. eLife 11, e81856 (2022).
Gasperini, M. et al. A genome-wide framework for mapping gene regulation via cellular genetic screens. Cell 176, 377–390.e19 (2019).
Yao, D. et al. Scalable genetic screening for regulatory circuits using compressed Perturb-seq. Nat. Biotechnol. 42, 1282–1295 (2024).
Morris, J. A. et al. Discovery of target genes and pathways at GWAS loci by pooled single-cell CRISPR screens. Science 380, eadh7699 (2023).
Datlinger, P. et al. Ultra-high-throughput single-cell RNA sequencing and perturbation screening with combinatorial fluidic indexing. Nat. Methods 18, 635–642 (2021).
Wu, B. et al. Overloading and unpacKing (OAK)—droplet-based combinatorial indexing for ultra-high throughput single-cell multiomic profiling. Nat. Commun. 15, 9146 (2024).
Wu, Q. et al. Massively parallel characterization of CRISPR activator efficacy in human induced pluripotent stem cells and neurons. Mol. Cell 83, 1125–1139.e8 (2023).
Loyfer, N. et al. A DNA methylation atlas of normal human cell types. Nature 613, 355–364 (2023).
Cazares, T. A. et al. maxATAC: genome-scale transcription-factor binding prediction from ATAC-seq with deep neural networks. PLoS Comput. Biol. 19, e1010863 (2023).
Tribolet-Hardy, J. et al. Genetic features and genomic targets of human KRAB-zinc finger proteins. Genome Res. 33, 1409–1423 (2023).
O’Geen, H., Henry, I. M., Bhakta, M. S., Meckler, J. F. & Segal, D. J. A genome-wide analysis of Cas9 binding specificity using ChIP-seq and targeted sequence capture. Nucleic Acids Res. 43, 3389–3404 (2015).
Rostain, W. et al. Cas9 off-target binding to the promoter of bacterial genes leads to silencing and toxicity. Nucleic Acids Res. 51, 3485–3496 (2023).
Uthaya et al. A genome-wide CRISPR activation screen identifies SCREEM a novel SNAI1 super-enhancer demarcated by eRNAs. Front. Mol. Biosci. 10, 1110445 (2023).
Nuñez, J. K. et al. Genome-wide programmable transcriptional memory by CRISPR-based epigenome editing. Cell 184, 2503–2519.e17 (2021).
Li, Y. et al. Genome-wide analyses reveal a role of Polycomb in promoting hypomethylation of DNA methylation valleys. Genome Biol. 19, 18 (2018).
Cui, A. et al. Dictionary of immune responses to cytokines at single-cell resolution. Nature 625, 377–384 (2024).
Fang, F. et al. Early growth response 3 (Egr-3) is induced by transforming growth factor-β and regulates fibrogenic responses. Am. J. Pathol. 183, 1197–1208 (2013).
Li, A. et al. GATA6 triggers fibroblast activation and tracheal fibrosis through the Wnt/β-catenin pathway. Cell. Signal. 105, 110593 (2023).
Stebler, S. & Raghunath, M. The Scar-in-a-Jar: In Vitro Fibrosis Model for Anti-Fibrotic Drug Testing. In Myofibroblasts: Methods and Protocols (eds. Hinz, B. & Lagares, D.) 147–156 (Springer, 2021). https://doi.org/10.1007/978-1-0716-1382-5_11
Vázquez-GarcÃa, I. et al. Ovarian cancer mutational processes drive site-specific immune evasion. Nature 612, 778–786 (2022).
Pollak, N. M., Hoffman, M., Goldberg, I. J. & Drosatos, K. Krüppel-like factors: crippling and uncrippling metabolic pathways. JACC Basic Transl. Sci. 3, 132–156 (2018).
Varrault, A. et al. Identification of Plagl1/Zac1 binding sites and target genes establishes its role in the regulation of extracellular matrix genes and the imprinted gene network. Nucleic Acids Res. 45, 10466–10480 (2017).
Jonsson, M. K. B. et al. A transcriptomic and epigenomic comparison of fetal and adult human cardiac fibroblasts reveals novel key transcription factors in adult cardiac fibroblasts. JACC Basic Transl. Sci. 1, 590–602 (2016).
Tsuda, T. et al. Zinc finger protein Zac1 is expressed in chondrogenic sites of the mouse. Dev. Dyn. 229, 340–348 (2004).
Chrysanthopoulou, A. et al. Down-regulation of KLF2 in lung fibroblasts is linked with COVID-19 immunofibrosis and restored by combined inhibition of NETs, JAK-1/2 and IL-6 signaling. Clin. Immunol. 247, 109240 (2023).
Shi, J. et al. KLF2 attenuates bleomycin-induced pulmonary fibrosis and inflammation with regulation of AP-1. Biochem. Biophys. Res. Commun. 495, 20–26 (2018).
Chandran, R. R. et al. Distinct roles of KLF4 in mesenchymal cell subtypes during lung fibrogenesis. Nat. Commun. 12, 7179 (2021).
Penke, L. R. et al. KLF4 is a therapeutically tractable brake on fibroblast activation that promotes resolution of pulmonary fibrosis. JCI Insight 7, e160688 (2022).
Noda, S. et al. Simultaneous downregulation of KLF5 and Fli1 is a key feature underlying systemic sclerosis. Nat. Commun. 5, 5797 (2014).
Roadmap Epigenomics Consortium et al. Integrative analysis of 111 reference human epigenomes. Nature 518, 317–330 (2015).
Wang, X. et al. Antibody-free profiling of transcription factor occupancy during early embryogenesis by FitCUT&RUN. Genome Res. 32, 378–388 (2022).
Southard, K. et al. Hs27-CRISPRa-TFs cellranger outputs. Zenodo https://doi.org/10.5281/ZENODO.15213597 (2025).
Southard, K. et al. Hs27-CRISPRa-TFs. Zenodo https://doi.org/10.5281/ZENODO.15200179 (2025).
Southard, K. et al. RPE1-CRISPRa-TFs cellranger outputs. Zenodo https://doi.org/10.5281/ZENODO.15211972 (2025).
Southard, K. et al. RPE1-CRISPRa-TFs. Zenodo https://doi.org/10.5281/ZENODO.15213619 (2025).
Southard, K. et al. RPE1-E150-Benchmarking cellranger outputs. Zenodo https://doi.org/10.5281/ZENODO.15215389 (2025).
Southard, K. et al. RPE1-E150-Benchmarking. Zenodo https://doi.org/10.5281/ZENODO.15215414 (2025).
Southard, K. et al. K562 dCas9-CUT&RUN. Zenodo https://doi.org/10.5281/ZENODO.15215154 (2025).
Southard, K. et al. RPE-1 and Hs27 CUT&RUN, ATAC-seq, and RNA-seq characterization. Zenodo https://doi.org/10.5281/ZENODO.15215216 (2025).
K. Southard & Norman, T. norman-lab-msk/TFs_CRISPRa: CRISPRa TFs Perturb-seq v0.1. Zenodo https://doi.org/10.5281/ZENODO.15373940 (2025).