Multiplexed 3D atlas of state transitions and immune interaction in colorectal cancer

Cell, Journal Year: 2023, Volume and Issue: 186(2), P. 363 - 381.e19

Published: Jan. 1, 2023

Advanced solid cancers are complex assemblies of tumor, immune, and stromal cells characterized by high intratumoral variation. We use highly multiplexed tissue imaging, 3D reconstruction, spatial statistics, machine learning to identify cell types states underlying morphological features known diagnostic prognostic significance in colorectal cancer. Quantitation these high-plex marker space reveals recurrent transitions from one tumor morphology the next, some which coincident with long-range gradients expression oncogenes epigenetic regulators. At invasive margin, where normal, immune compete, T suppression involves multiple imaging shows that seemingly localized 2D such as tertiary lymphoid structures commonly interconnected have graded molecular properties. Thus, while cancer genetics emphasizes importance discrete changes state, whole-specimen large-scale analogous those developing tissues.

Language: Английский

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MCMICRO: a scalable, modular image-processing pipeline for multiplexed tissue imaging

Nature Methods, Journal Year: 2021, Volume and Issue: 19(3), P. 311 - 315

Published: Nov. 25, 2021

Highly multiplexed tissue imaging makes detailed molecular analysis of single cells possible in a preserved spatial context. However, reproducible large multichannel images poses substantial computational challenge. Here, we describe modular and open-source pipeline, MCMICRO, for performing the sequential steps needed to transform whole-slide into single-cell data. We demonstrate use MCMICRO on tumor acquired using multiple platforms, thereby providing solid foundation continued development software.

Language: Английский

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An end-to-end workflow for multiplexed image processing and analysis

Nature Protocols, Journal Year: 2023, Volume and Issue: 18(11), P. 3565 - 3613

Published: Oct. 10, 2023

Language: Английский

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Spatial single-cell mass spectrometry defines zonation of the hepatocyte proteome

Nature Methods, Journal Year: 2023, Volume and Issue: 20(10), P. 1530 - 1536

Published: Oct. 1, 2023

Single-cell proteomics by mass spectrometry is emerging as a powerful and unbiased method for the characterization of biological heterogeneity. So far, it has been limited to cultured cells, whereas an expansion complex tissues would greatly enhance insights. Here we describe single-cell Deep Visual Proteomics (scDVP), technology that integrates high-content imaging, laser microdissection multiplexed spectrometry. scDVP resolves context-dependent, spatial proteome murine hepatocytes at current depth 1,700 proteins from cell slice. Half was differentially regulated in manner, with protein levels changing dramatically proximity central vein. We applied machine learning classes images, which subsequently inferred imaging data alone. applicable healthy diseased complements other omics technologies.

Language: Английский

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High-plex immunofluorescence imaging and traditional histology of the same tissue section for discovering image-based biomarkers

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

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Lymphocyte networks are dynamic cellular communities in the immunoregulatory landscape of lung adenocarcinoma

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

Published: April 13, 2023

Language: Английский

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Multiplexed, image-based pooled screens in primary cells and tissues with PerturbView

Nature Biotechnology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 7, 2024

Language: Английский

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Evolutionary convergence of sensory circuits in the pallium of amniotes

Science, Journal Year: 2025, Volume and Issue: 387(6735)

Published: Jan. 2, 2025

The amniote pallium contains sensory circuits that are structurally and functionally equivalent, yet their evolutionary relationship remains unresolved. We used birthdating analysis, single-cell RNA spatial transcriptomics, mathematical modeling to compare the development evolution of known pallial across birds (chick), lizards (gecko), mammals (mouse). reveal neurons within these circuits’ stations generated at varying developmental times brain regions species found an early divergence in transcriptomic progression glutamatergic neurons. Our research highlights distinctions functional similarities circuit between mammals, suggesting convergence high-order processing lineages.

Language: Английский

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Age-dependent regulation of SARS-CoV-2 cell entry genes and cell death programs correlates with COVID-19 severity

Science Advances, Journal Year: 2021, Volume and Issue: 7(34)

Published: Aug. 18, 2021

Changes in lung ACE2 expression and apoptotic priming throughout life span may affect COVID severity.

Language: Английский

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Temporal and spatial topography of cell proliferation in cancer

Nature Cell Biology, Journal Year: 2022, Volume and Issue: 24(3), P. 316 - 326

Published: March 1, 2022

Language: Английский

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