Single cell spatial analysis reveals the topology of immunomodulatory purinergic signaling in glioblastoma DOI Creative Commons
Shannon Coy, Shu Wang, Sylwia A. Stopka

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Aug. 16, 2022

How the glioma immune microenvironment fosters tumorigenesis remains incompletely defined. Here, we use single-cell RNA-sequencing and multiplexed tissue-imaging to characterize composition, spatial organization, clinical significance of extracellular purinergic signaling in glioma. We show that microglia are predominant source CD39, while tumor cells principally express CD73. In glioblastoma, CD73 is associated with EGFR amplification, astrocyte-like differentiation, increased adenosine, linked hypoxia. Glioblastomas enriched for exhibit inflammatory microenvironments, suggesting regulates adaptation. Spatially-resolved analyses demonstrate a strong correlation between tumor-CD73 microglial-CD39, proximity poor outcomes. Similar organization present pediatric high-grade gliomas including H3K27M-mutant diffuse midline These data reveal shaped by genotype, lineage, functional state, core enzymes expressed myeloid organized promote adenosine-rich microenvironments potentially amenable therapeutic targeting.

Language: Английский

An introduction to spatial transcriptomics for biomedical research DOI Creative Commons

Cameron G. Williams,

Hyun Jae Lee,

Takahiro Asatsuma

et al.

Genome Medicine, Journal Year: 2022, Volume and Issue: 14(1)

Published: June 27, 2022

Abstract Single-cell transcriptomics (scRNA-seq) has become essential for biomedical research over the past decade, particularly in developmental biology, cancer, immunology, and neuroscience. Most commercially available scRNA-seq protocols require cells to be recovered intact viable from tissue. This precluded many cell types study largely destroys spatial context that could otherwise inform analyses of identity function. An increasing number platforms now facilitate spatially resolved, high-dimensional assessment gene transcription, known as ‘spatial transcriptomics’. Here, we introduce different classes method, which either record locations hybridized mRNA molecules tissue, image positions themselves prior assessment, or employ arrays probes pre-determined location. We review sizes tissue area can assessed, their resolution, genes profiled. discuss if preservation influences choice platform, provide guidance on whether specific may better suited discovery screens hypothesis testing. Finally, bioinformatic methods analysing transcriptomic data, including pre-processing, integration with existing inference cell-cell interactions. Spatial -omics are already improving our understanding human tissues research, diagnostic, therapeutic settings. To build upon these recent advancements, entry-level those seeking own research.

Language: Английский

Citations

462
The Spatial Landscape of Progression and Immunoediting in Primary Melanoma at Single-Cell Resolution DOI Creative Commons
Ajit J. Nirmal, Zoltan Maliga, Tuulia Vallius

et al.

Cancer Discovery, Journal Year: 2022, Volume and Issue: 12(6), P. 1518 - 1541

Published: April 4, 2022

Cutaneous melanoma is a highly immunogenic malignancy that surgically curable at early stages but life-threatening when metastatic. Here we integrate high-plex imaging, 3D high-resolution microscopy, and spatially resolved microregion transcriptomics to study immune evasion immunoediting in primary melanoma. We find recurrent cellular neighborhoods involving tumor, immune, stromal cells change significantly along progression axis precursor states, situ, invasive tumor. Hallmarks of immunosuppression are already detectable regions. When tumors become locally invasive, consolidated restricted suppressive environment forms the tumor-stromal boundary. This established by cytokine gradients promote expression MHC-II IDO1, PD1-PDL1-mediated cell contacts macrophages, dendritic cells, T cells. A few millimeters away, cytotoxic synapse with fields tumor regression. Thus, invasion can coexist within each other single specimen. The reorganization ecosystem an excellent setting which evasion. Guided classic histopathology, spatial profiling proteins mRNA reveals morphologic molecular features evolution involve localized paracrine signaling direct cell-cell contact. article highlighted In Issue feature, p. 1397.

Language: Английский

Citations

160
Stitching and registering highly multiplexed whole-slide images of tissues and tumors using ASHLAR DOI Creative Commons
Jeremy Muhlich, Yu‐An Chen, Clarence Yapp

et al.

Bioinformatics, Journal Year: 2022, Volume and Issue: 38(19), P. 4613 - 4621

Published: Aug. 16, 2022

Abstract Motivation Stitching microscope images into a mosaic is an essential step in the analysis and visualization of large biological specimens, particularly human animal tissues. Recent approaches to highly multiplexed imaging generate high-plex data from sequential rounds lower-plex imaging. These methods promise yield precise molecular single-cell information on cellular neighborhoods tissue architecture. However, attaining with accuracy requires robust image stitching registration capabilities that are not met by existing methods. Results We describe development testing ASHLAR, Python tool for coordinated 103 or more individual accurate whole-slide mosaics. ASHLAR reads formats most commercial microscopes slide scanners, we show it performs better than open-source software. outputs standard OME-TIFF ready other tools recently developed pipelines. Availability implementation written available under MIT license at https://github.com/labsyspharm/ashlar. The newly published underlying this article Sage Synapse https://dx.doi.org/10.7303/syn25826362; availability previously re-analyzed described Supplementary Table S4. An informational website user guides test https://labsyspharm.github.io/ashlar/. Bioinformatics online.

Language: Английский

Citations

82
Spatial multi-omics analyses of the tumor immune microenvironment DOI Creative Commons
Wan-Chen Hsieh,

Bugi Ratno Budiarto,

Yi‐Fu Wang

et al.

Journal of Biomedical Science, Journal Year: 2022, Volume and Issue: 29(1)

Published: Nov. 14, 2022

Abstract In the past decade, single-cell technologies have revealed heterogeneity of tumor-immune microenvironment at genomic, transcriptomic, and proteomic levels furthered our understanding mechanisms tumor development. Single-cell also been used to identify potential biomarkers. However, spatial information about such as cell locations cell–cell interactomes is lost in these approaches. Recently, multi-omics study transcriptomes, proteomes, metabolomes microenvironments several types cancer, data obtained from methods has combined with immunohistochemistry multiparameter analysis yield markers cancer progression. Here, we review numerous cutting-edge ‘omics techniques, their application microenvironment, remaining technical challenges.

Language: Английский

Citations

76
Tumor-associated macrophages trigger MAIT cell dysfunction at the HCC invasive margin DOI Creative Commons
Benjamin Ruf,

Matthias Bruhns,

Sepideh Babaei

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(17), P. 3686 - 3705.e32

Published: Aug. 1, 2023

Language: Английский

Citations

76
High-plex immunofluorescence imaging and traditional histology of the same tissue section for discovering image-based biomarkers DOI Creative Commons
Jia‐Ren Lin, Chen Yuan, Daniel Campton

et al.

Nature Cancer, Journal Year: 2023, Volume and Issue: 4(7), P. 1036 - 1052

Published: June 22, 2023

Precision medicine is critically dependent on better methods for diagnosing and staging disease predicting drug response. Histopathology using hematoxylin eosin (H&E)-stained tissue (not genomics) remains the primary diagnostic method in cancer. Recently developed highly multiplexed imaging promise to enhance research studies clinical practice with precise, spatially resolved single-cell data. Here, we describe 'Orion' platform collecting H&E high-plex immunofluorescence images from same cells a whole-slide format suitable diagnosis. Using retrospective cohort of 74 colorectal cancer resections, show that provide human experts machine learning algorithms complementary information can be used generate interpretable, image-based models predictive progression-free survival. Combining immune infiltration tumor-intrinsic features achieves 10- 20-fold discrimination between rapid slow (or no) progression, demonstrating ability multimodal high-performance biomarkers.

Language: Английский

Citations

74
Inferring super-resolution tissue architecture by integrating spatial transcriptomics with histology DOI
Daiwei Zhang,

Amelia Schroeder,

Hanying Yan

et al.

Nature Biotechnology, Journal Year: 2024, Volume and Issue: 42(9), P. 1372 - 1377

Published: Jan. 2, 2024

Language: Английский

Citations

68
Decoding the tumor microenvironment with spatial technologies DOI
Logan A. Walsh,

Daniela F. Quail

Nature Immunology, Journal Year: 2023, Volume and Issue: 24(12), P. 1982 - 1993

Published: Nov. 27, 2023

Language: Английский

Citations

60
Lymphocyte networks are dynamic cellular communities in the immunoregulatory landscape of lung adenocarcinoma DOI Creative Commons
Giorgio Gaglia, Megan L. Burger, Cecily C. Ritch

et al.

Cancer Cell, Journal Year: 2023, Volume and Issue: 41(5), P. 871 - 886.e10

Published: April 13, 2023

Language: Английский

Citations

51
SOX17 enables immune evasion of early colorectal adenomas and cancers DOI

Norihiro Goto,

Peter M.K. Westcott, Saori Goto

et al.

Nature, Journal Year: 2024, Volume and Issue: 627(8004), P. 636 - 645

Published: Feb. 28, 2024

Language: Английский

Citations

43