Cited by Considerations for building and using integrated single-cell atlases

Influenza vaccine format mediates distinct cellular and antibody responses in human immune organoids DOI

Jenna M. Kastenschmidt, Suhas Sureshchandra, Aarti Jain

et al.

Immunity, Journal Year: 2023, Volume and Issue: 56(8), P. 1910 - 1926.e7

Published: July 20, 2023

Highly effective vaccines elicit specific, robust, and durable adaptive immune responses. To advance informed vaccine design, it is critical that we understand the cellular dynamics underlying responses to different antigen formats. Here, sought how antigen-specific B T cells were activated participated in within mucosal site. Using a human tonsil organoid model, tracked differentiation kinetics of response influenza virus modalities. Each format elicited distinct cell responses, including differences their magnitude, diversity, phenotype, function, breadth. These culminated substantial changes corresponding antibody response. A major source format-related variability was ability recruit naive vs. memory findings have important implications for design generation protective upper respiratory tract.

Language: Английский

Citations

The future of rapid and automated single-cell data analysis using reference mapping DOI

Mohammad Lotfollahi, Yuhan Hao, Fabian J. Theis

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(10), P. 2343 - 2358

Published: May 1, 2024

As the number of single-cell datasets continues to grow rapidly, workflows that map new data well-curated reference atlases offer enormous promise for biological community. In this perspective, we discuss key computational challenges and opportunities reference-mapping algorithms. We how mapping algorithms will enable integration diverse across disease states, molecular modalities, genetic perturbations, species eventually replace manual laborious unsupervised clustering pipelines.

Language: Английский

Citations

Spatially-resolved transcriptomics reveal macrophage heterogeneity and prognostic significance in diffuse large B-cell lymphoma DOI

Min Liu, Giorgio Bertolazzi, Shruti Sridhar

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 8, 2024

Abstract Macrophages are abundant immune cells in the microenvironment of diffuse large B-cell lymphoma (DLBCL). Macrophage estimation by immunohistochemistry shows varying prognostic significance across studies DLBCL, and does not provide a comprehensive analysis macrophage subtypes. Here, using digital spatial profiling with whole transcriptome CD68+ cells, we characterize macrophages distinct niches reactive lymphoid tissues (RLTs) DLBCL. We reveal transcriptomic differences between within RLTs (light zone /dark zone, germinal center/ interfollicular), disease states (RLTs/ DLBCL), which then use to generate six spatially-derived signatures (MacroSigs). proceed interrogate these MacroSigs DLBCL single-cell RNA-sequencing datasets, gene-expression data from multiple cohorts. show that specific associated cell-of-origin subtypes overall survival This study provides spatially-resolved whole-transcriptome atlas malignant tissues, showing biological clinical significance.

Language: Английский

Citations

Targeting the immune privilege of tumor-initiating cells to enhance cancer immunotherapy DOI

Chen Yang, Haigang Geng, Xupeng Yang

et al.

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(12), P. 2064 - 2081.e19

Published: Nov. 7, 2024

Language: Английский

Citations

Intratumor heterogeneity of HPV integration in HPV-associated head and neck cancer DOI

Noah Sasa, Toshihiro Kishikawa,

Masashi Mori

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 26, 2025

Integration of human papillomavirus (HPV) into the host genome drives HPV-positive head and neck squamous cell carcinoma (HPV+ HNSCC). Whole-genome sequencing 51 tumors revealed intratumor heterogeneity HPV integration, with 44% breakpoints subclonal, a biased distribution integration across genome. Four physical states were identified, at least 49% progressing without integration. was associated APOBEC-induced broad genomic instability focal instability, including structural variants sites. HPV+ HNSCCs exhibited almost no smoking-induced mutational signatures. Heterozygous loss ataxia-telangiectasia mutated (ATM) observed in 67% tumors, its downregulation confirmed by single-cell RNA immunohistochemistry, suggesting ATM haploinsufficiency contributes to carcinogenesis. PI3K activation major oncogenic mutation, JAK-STAT clonal NF-kappa B those without. These findings provide valuable insights HNSCC. The Here, authors perform analysis investigate patients HNSCC, identifying

Language: Английский

Citations

Unveiling spatial complexity in solid tumor immune microenvironments through multiplexed imaging DOI

Sophia Scheuermann, Beate Kristmann,

F. Engelmann

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: March 19, 2024

Deciphering cellular components and the spatial interaction network of tumor immune microenvironment (TIME) solid tumors is pivotal for understanding biologically relevant cross-talks and, ultimately, advancing therapies. Multiplexed tissue imaging provides a powerful tool to elucidate complexity in holistic manner. We established cross-validated comprehensive immunophenotyping panel comprising over 121 markers multiplexed using MACSima™ cyclic staining (MICS) alongside an end-to-end analysis workflow. Applying this workflow primary cancer tissues, we characterized heterogeneity, investigated potential therapeutical targets, conducted in-depth profiling cell types states, sub-phenotyped T cells within TIME, scrutinized neighborhoods diverse subsets. Our findings highlight advantage profiling, revealing immunosuppressive molecular signatures tumor-associated myeloid interacting with neighboring exhausted, PD1 high TIME hepatocellular carcinoma (HCC). This study establishes robust framework exploration TIMEs underscores potency ultra-deep phenotyping unraveling clinically components.

Language: Английский

Citations

RORγt-dependent antigen-presenting cells direct regulatory T cell-mediated tolerance to food antigen DOI

Liuhui Fu, Rabi Upadhyay, Maria Pokrovskii

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 24, 2024

Abstract The gastrointestinal tract is continuously exposed to foreign antigens in food and commensal microbes with potential induce adaptive immune responses. Peripherally induced T regulatory (pTreg) cells are essential for mitigating inflammatory responses these agents 1–4 . While RORγt + antigen-presenting (RORγt-APCs) were shown program gut microbiota-specific pTreg 5–7 , their definition remains incomplete, the APC responsible tolerance has remained elusive. Here, we identify a distinct subset of RORγt-APCs, designated tolerogenic dendritic (tDC), required differentiation both food- establishment oral tolerance. tDC development function require expression transcription factors Prdm16 RORγt, as well unique Rorc(t) cis-regulatory element. Gene expression, chromatin accessibility, surface marker analysis establish myeloid origin, from ILC3, sharing epigenetic profiles classical DC. Upon genetic perturbation tDC, observe substantial increase antigen-specific helper 2 (Th2) lieu pTreg, leading compromised mouse models asthma allergy. Single-cell analyses freshly resected mesenteric lymph nodes human organ donor, multiple specimens intestine tonsil, reveal candidate co-expression PRDM16 RORC an extensive transcriptome shared mice, highlighting evolutionarily conserved role across species. Our findings suggest that better understanding how develop they regulate cell microbial could offer new insights into developing therapeutic strategies autoimmune allergic diseases transplant

Language: Английский

Citations

A platinum polymer probe for multiplexed single cell suspension mass cytometry and imaging mass cytometry assays DOI

Edmond C. N. Wong, Tianjia Yang, Yefeng Zhang

et al.

Chemical Engineering Journal, Journal Year: 2025, Volume and Issue: unknown, P. 159745 - 159745

Published: Jan. 1, 2025

Language: Английский

Citations

Boosting human immunology: harnessing the potential of immune organoids DOI

Maximilian Moll, Dirk Baumjohann

EMBO Molecular Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 27, 2025

Language: Английский

Citations

A Temporal and Spatial Atlas of Adaptive Immune Responses in the Lymph Node Following Viral Infection DOI

Shaowen Jiang, Madhav Mantri, Viviana I. Maymí

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 6, 2025

ABSTRACT The spatial organization of adaptive immune cells within lymph nodes is critical for understanding responses during infection and disease. Here, we introduce AIR-SPACE, an integrative approach that combines high-resolution transcriptomics with paired, high-fidelity long-read sequencing T B cell receptors. This method enables the simultaneous analysis cellular transcriptomes receptor (AIR) repertoires their native context. We applied AIR-SPACE to mouse popliteal at five distinct time points after Vaccinia virus footpad constructed a comprehensive map developing response. Our revealed heterogeneous activation niches, characterized by Interferon-gamma (IFN-γ) production, early stages infection. At later stages, delineated sub-anatomical structures germinal center (GC) observed evidence antibody-producing plasma differentiate exit GC through dark zone. Furthermore, combining clonotype data lineage tracing, demonstrate clones are shared among multiple GCs same node, reinforcing concept dynamic, interconnected network GCs. Overall, our study demonstrates how can be used gain insight into dynamics lymphoid organs.

Language: Английский

Citations