ArticleNature genetics2025
Comprehensive transcription factor perturbations recapitulate fibroblast transcriptional states.
Article in Nature genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Article
- Cardiac fibroblast diversity in HFpEF: states, niches, interorgan drivers and targets.Nature reviews. Cardiology · 2026Review
- Single-cell multimodal profiling of pan-cancer cell lines uncovers gene regulatory principles underlying intrinsic cell states and environmental features.Nature communications · 2026Article
- Unleashing innovative cross-organ fibrosis therapies by harnessing the omics revolution.JCI insight · 2026Review
- Region-Level Design and Analysis of CRISPR Perturbation Screens with FRACTEL.bioRxiv : the preprint server for biology · 2026Article
- ILC2s regulate a fibroblast progenitor niche in the pancreas.Science (New York, N.Y.) · 2026Article
- Neurodevelopmental Disorder with Dystonia and Chorea Linked to De Novo Variants in the Splicing Regulator SRRM4.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Single-cell multimodal profiling of pan-cancer cell lines uncovers gene regulatory principles underlying intrinsic cell states and environmental features.bioRxiv : the preprint server for biology · 2026Article
- An autochthonous CRISPR activation screening platform for characterizing tissue-specific oncogene selection.Cell reports. Medicine · 2026Article
- Parallel Activation and Interference CRISPR (PAIR) with Sequencing Uncovers DNA Repair Networks Guiding Precision Cell Engineering.bioRxiv : the preprint server for biology · 2026Article
- Elucidating genes sufficient for viral entry into cells through sequential genome-wide CRISPR activation screens.bioRxiv : the preprint server for biology · 2026Article
- PARP1 Suppression Drives ROS Resistance in Aneuploid Cancer Cells.bioRxiv : the preprint server for biology · 2026Article
- Mismatch tolerance of a gRNA for CRISPR-based gene activation confers broad activity critical for cell reprogramming.bioRxiv : the preprint server for biology · 2026Article
- Fibroblast heterogeneity in 2025.Nature reviews. Rheumatology · 2026Article
- Large-scale discovery of neural enhancers for cis-regulation therapies.bioRxiv : the preprint server for biology · 2025Article
- AI-powered programmable virtual humans toward human physiologically-based drug discovery.Drug discovery today · 2025Review
- A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues.Nature immunology · 2025Article
- Article
- Genome-wide CRISPR guide RNA design and specificity analysis with GuideScan2.Genome biology · 2025Article
- Multiome Perturb-seq unlocks scalable discovery of integrated perturbation effects on the transcriptome and epigenome.Cell systems · 2025Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Cell atlas projects have revealed that common cell types often comprise distinct, recurrent transcriptional states, but the function and regulation of these states remain poorly understood. Here, we show that systematic activation of transcription factors can recreate such states in vitro, providing tractable models for mechanistic and functional studies. Using a scalable CRISPR activation (CRISPRa) Perturb-seq platform, we activated 1,836 transcription factors in two cell types. CRISPRa induced gene expression within physiological ranges, with chromatin features predicting responsiveness. Comparisons with atlas datasets showed that transcription factor perturbations recapitulated key fibroblast states and identified their regulators, including KLF2 and KLF4 for a universal state present in many tissues, and PLAGL1 for a disease-associated inflammatory state. Inducing the universal state suppressed the inflammatory state, suggesting therapeutic potential. These findings position CRISPRa as a nuanced tool for perturbing differentiated cells and establish a general strategy for studying clinically relevant transcriptional states ex vivo.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.