
Laboratory Investigation, Journal Year: 2022, Volume and Issue: 102(7), P. 762 - 770
Published: March 30, 2022
Language: Английский
Laboratory Investigation, Journal Year: 2022, Volume and Issue: 102(7), P. 762 - 770
Published: March 30, 2022
Language: Английский
Nature Reviews Microbiology, Journal Year: 2022, Volume and Issue: 20(12), P. 750 - 766
Published: July 25, 2022
Language: Английский
Citations
312Science, Journal Year: 2023, Volume and Issue: 381(6657)
Published: Aug. 3, 2023
Spatial omics has been widely heralded as the new frontier in life sciences. This term encompasses a wide range of techniques that promise to transform many areas biology and eventually revolutionize pathology by measuring physical tissue structure molecular characteristics at same time. Although field came age past 5 years, it still suffers from some growing pains: barriers entry, robustness, unclear best practices for experimental design analysis, lack standardization. In this Review, we present systematic catalog different families spatial technologies; highlight their principles, power, limitations; give perspective suggestions on biggest challenges lay ahead incredibly powerful-but hard navigate-landscape.
Language: Английский
Citations
256Cancer Cell, Journal Year: 2023, Volume and Issue: 41(3), P. 404 - 420
Published: Feb. 16, 2023
Language: Английский
Citations
210Immunity, Journal Year: 2022, Volume and Issue: 55(5), P. 827 - 846.e10
Published: April 27, 2022
Mycobacterium tuberculosis lung infection results in a complex multicellular structure: the granuloma. In some granulomas, immune activity promotes bacterial clearance, but others, bacteria persist and grow. We identified correlates of control cynomolgus macaque granulomas by co-registering longitudinal positron emission tomography computed imaging, single-cell RNA sequencing, measures clearance. Bacterial persistence occurred enriched for mast, endothelial, fibroblast, plasma cells, signaling amongst themselves via type 2 immunity wound-healing pathways. Granulomas that drove were characterized cellular ecosystems 1-type 17, stem-like, cytotoxic T cells engaged pro-inflammatory networks involving diverse cell populations. arose later displayed functional characteristics restrictive more capable killing Mtb. Our define underlying (lack of) granuloma resolution highlight host targets can be leveraged to develop new vaccine therapeutic strategies TB.
Language: Английский
Citations
180Nature Reviews Genetics, Journal Year: 2022, Volume and Issue: 24(5), P. 295 - 313
Published: Dec. 9, 2022
Language: Английский
Citations
119Nature, Journal Year: 2023, Volume and Issue: 619(7970), P. 595 - 605
Published: July 19, 2023
Abstract Beginning in the first trimester, fetally derived extravillous trophoblasts (EVTs) invade uterus and remodel its spiral arteries, transforming them into large, dilated blood vessels. Several mechanisms have been proposed to explain how EVTs coordinate with maternal decidua promote a tissue microenvironment conducive artery remodelling (SAR) 1–3 . However, it remains matter of debate regarding which immune stromal cells participate these interactions this evolves respect gestational age. Here we used multiomics approach, combining strengths spatial proteomics transcriptomics, construct spatiotemporal atlas human maternal–fetal interface half pregnancy. We multiplexed ion beam imaging by time-of-flight 37-plex antibody panel analyse around 500,000 588 arteries within intact from 66 individuals between 6 20 weeks gestation, integrating dataset co-registered transcriptomics profiles. Gestational age substantially influenced frequency cells, tolerogenic subsets expressing CD206, CD163, TIM-3, galectin-9 IDO-1 becoming increasingly enriched colocalized at later time points. By contrast, SAR progression preferentially correlated EVT invasion was transcriptionally defined 78 gene ontology pathways exhibiting distinct monotonic biphasic trends. Last, developed an integrated model whereby is accompanied upregulation pro-angiogenic, immunoregulatory programmes that vascular endothelium while avoiding activation cells.
Language: Английский
Citations
83Cell, Journal Year: 2022, Volume and Issue: 185(25), P. 4682 - 4702
Published: Dec. 1, 2022
Language: Английский
Citations
76Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)
Published: Aug. 1, 2023
Abstract While technologies for multiplexed imaging have provided an unprecedented understanding of tissue composition in health and disease, interpreting this data remains a significant computational challenge. To understand the spatial organization how it relates to disease processes, studies typically focus on cell-level phenotypes. However, images can capture biologically important objects that are outside cells, such as extracellular matrix. Here, we describe pipeline, Pixie, achieves robust quantitative annotation pixel-level features using unsupervised clustering show its application across variety biological contexts platforms. Furthermore, current cell phenotyping strategies rely be labor intensive require large amounts manual cluster adjustments. We demonstrate pixel clusters lie within cells used improve annotations. comprehensively evaluate pre-processing steps parameter choices optimize performance quantify reproducibility our method. Importantly, Pixie is open source easily customizable through user-friendly interface.
Language: Английский
Citations
51Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)
Published: May 15, 2023
Abstract Spatial proteomics technologies have revealed an underappreciated link between the location of cells in tissue microenvironments and underlying biology clinical features, but there is significant lag development downstream analysis methods benchmarking tools. Here we present SPIAT (spatial image tissues), a spatial-platform agnostic toolkit with suite spatial algorithms, spaSim simulator), simulator data. includes multiple colocalization, neighborhood heterogeneity metrics to characterize patterns cells. Ten are benchmarked using simulated data generated spaSim. We show how can uncover cancer immune subtypes correlated prognosis cell dysfunction diabetes. Our results suggest as useful tools for quantifying patterns, identifying validating correlates outcomes supporting method development.
Language: Английский
Citations
50Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)
Published: July 18, 2023
Abstract Multiplexed imaging enables measurement of multiple proteins in situ, offering an unprecedented opportunity to chart various cell types and states tissues. However, classification, the task identifying type individual cells, remains challenging, labor-intensive, limiting throughput. Here, we present CellSighter, a deep-learning based pipeline accelerate classification multiplexed images. Given small training set expert-labeled images, CellSighter outputs label probabilities for all cells new achieves over 80% accuracy major across platforms, which approaches inter-observer concordance. Ablation studies simulations show that is able generalize its data learn features protein expression levels, as well spatial such subcellular patterns. CellSighter’s design reduces overfitting, it can be trained with only thousands or even hundreds labeled examples. also prediction confidence, allowing downstream experts control results. Altogether, drastically hands-on time while improving consistency datasets.
Language: Английский
Citations
49