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BACH2 regulates diversification of regulatory and proinflammatory chromatin states in TH17 cells
Interleukin-17 (IL-17)-producing helper T (TH17) cells are heterogenous and consist of nonpathogenic TH17 (npTH17) cells that contribute to tissue homeostasis and pathogenic TH17 (pTH17) cells that mediate tissue...
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Article
Open AccessSystematic benchmarking of single-cell ATAC-sequencing protocols
Single-cell assay for transposase-accessible chromatin by sequencing (scATAC-seq) has emerged as a powerful tool for dissecting regulatory landscapes and cellular heterogeneity. However, an exploration of syst...
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Article
Open AccessAn esophagus cell atlas reveals dynamic rewiring during active eosinophilic esophagitis and remission
Coordinated cell interactions within the esophagus maintain homeostasis, and disruption can lead to eosinophilic esophagitis (EoE), a chronic inflammatory disease with poorly understood pathogenesis. We profil...
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Cell subtype-specific effects of genetic variation in the Alzheimer’s disease brain
The relationship between genetic variation and gene expression in brain cell types and subtypes remains understudied. Here, we generated single-nucleus RNA sequencing data from the neocortex of 424 individuals...
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Open AccessTACCO unifies annotation transfer and decomposition of cell identities for single-cell and spatial omics
Transferring annotations of single-cell-, spatial- and multi-omics data is often challenging owing both to technical limitations, such as low spatial resolution or high dropout fraction, and to biological vari...
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Article
B-cell-specific checkpoint molecules that regulate anti-tumour immunity
The role of B cells in anti-tumour immunity is still debated and, accordingly, immunotherapies have focused on targeting T and natural killer cells to inhibit tumour growth1,2. Here, using high-throughput flow cy...
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Article
Multicellular communities are perturbed in the aging human brain and Alzheimer’s disease
The role of different cell types and their interactions in Alzheimer’s disease (AD) is a complex and open question. Here, we pursued this question by assembling a high-resolution cellular map of the aging fron...
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Article
Open AccessAn integrated cell atlas of the lung in health and disease
Single-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number of donors and disagree on cell type definitions. Integrating many single-cell ...
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Article
Open AccessMostly natural sequencing-by-synthesis for scRNA-seq using Ultima sequencing
Here we introduce a mostly natural sequencing-by-synthesis (mnSBS) method for single-cell RNA sequencing (scRNA-seq), adapted to the Ultima genomics platform, and systematically benchmark it against current sc...
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Article
Author Correction: Massively parallel phenoty** of coding variants in cancer with Perturb-seq
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Single-nucleus and spatial transcriptome profiling of pancreatic cancer identifies multicellular dynamics associated with neoadjuvant treatment
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal and treatment-refractory cancer. Molecular stratification in pancreatic cancer remains rudimentary and does not yet inform clinical management or ther...
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Article
Open AccessMouse fetal growth restriction through parental and fetal immune gene variation and intercellular communications cascade
Fetal growth restriction (FGR) affects 5–10% of pregnancies, and can have serious consequences for both mother and child. Prevention and treatment are limited because FGR pathogenesis is poorly understood. Gen...
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Article
Massively parallel phenoty** of coding variants in cancer with Perturb-seq
Genome sequencing studies have identified millions of somatic variants in cancer, but it remains challenging to predict the phenotypic impact of most. Experimental approaches to distinguish impactful variants ...
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Article
Epigenetic encoding, heritability and plasticity of glioma transcriptional cell states
Single-cell RNA sequencing has revealed extensive transcriptional cell state diversity in cancer, often observed independently of genetic heterogeneity, raising the central question of how malignant cell state...
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Article
Blood and immune development in human fetal bone marrow and Down syndrome
Haematopoiesis in the bone marrow (BM) maintains blood and immune cell production throughout postnatal life. Haematopoiesis first emerges in human BM at 11–12 weeks after conception1,2, yet almost nothing is know...
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Open AccessA human liver cell-based system modeling a clinical prognostic liver signature for therapeutic discovery
Chronic liver disease and hepatocellular carcinoma (HCC) are life-threatening diseases with limited treatment options. The lack of clinically relevant/tractable experimental models hampers therapeutic discover...
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Article
A roadmap for the Human Developmental Cell Atlas
The Human Developmental Cell Atlas (HDCA) initiative, which is part of the Human Cell Atlas, aims to create a comprehensive reference map of cells during development. This will be critical to understanding nor...
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Article
TIM-3 restrains anti-tumour immunity by regulating inflammasome activation
T cell immunoglobulin and mucin-containing molecule 3 (TIM-3), first identified as a molecule expressed on interferon-γ producing T cells1, is emerging as an important immune-checkpoint molecule, with therapeutic...
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Article
COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets
COVID-19, which is caused by SARS-CoV-2, can result in acute respiratory distress syndrome and multiple organ failure1–4, but little is known about its pathophysiology. Here we generated single-cell atlases of 24...
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Open AccessTranscriptional mediators of treatment resistance in lethal prostate cancer
Metastatic castration-resistant prostate cancer is typically lethal, exhibiting intrinsic or acquired resistance to second-generation androgen-targeting therapies and minimal response to immune checkpoint inhi...