Cell2location maps fine-grained cell types in spatial transcriptomics

Nature Biotechnology, Journal Year: 2022, Volume and Issue: 40(5), P. 661 - 671

Published: Jan. 13, 2022

Language: Английский

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An introduction to spatial transcriptomics for biomedical research

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

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Comparison of methods and resources for cell-cell communication inference from single-cell RNA-Seq data

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

Published: June 9, 2022

Abstract The growing availability of single-cell data, especially transcriptomics, has sparked an increased interest in the inference cell-cell communication. Many computational tools were developed for this purpose. Each them consists a resource intercellular interactions prior knowledge and method to predict potential communication events. Yet impact choice on resulting predictions is largely unknown. To shed light this, we systematically compare 16 resources 7 methods, plus consensus between methods’ predictions. Among resources, find few unique interactions, varying degree overlap, uneven coverage specific pathways tissue-enriched proteins. We then examine all possible combinations methods show that both strongly influence predicted interactions. Finally, assess agreement with spatial colocalisation, cytokine activities, receptor protein abundance are generally coherent those data modalities. facilitate use described work, provide LIANA, LIgand-receptor ANalysis frAmework as open-source interface methods.

Language: Английский

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High-resolution single-cell atlas reveals diversity and plasticity of tissue-resident neutrophils in non-small cell lung cancer

Cancer Cell, Journal Year: 2022, Volume and Issue: 40(12), P. 1503 - 1520.e8

Published: Nov. 10, 2022

Non-small cell lung cancer (NSCLC) is characterized by molecular heterogeneity with diverse immune infiltration patterns, which has been linked to therapy sensitivity and resistance. However, full understanding of how phenotypes vary across different patient subgroups lacking. Here, we dissect the NSCLC tumor microenvironment at high resolution integrating 1,283,972 single cells from 556 samples 318 patients 29 datasets, including our dataset capturing low mRNA content. We stratify into immune-deserted, B cell, T myeloid subtypes. Using bulk genomic clinical information, identify cellular components associated histology genotypes. then focus on analysis tissue-resident neutrophils (TRNs) uncover distinct subpopulations that acquire new functional properties in tissue microenvironment, providing evidence for plasticity TRNs. Finally, show a TRN-derived gene signature anti-programmed death ligand 1 (PD-L1) treatment failure.

Language: Английский

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Mapping the developing human immune system across organs

Science, Journal Year: 2022, Volume and Issue: 376(6597)

Published: May 12, 2022

Single-cell genomics studies have decoded the immune cell composition of several human prenatal organs but were limited in describing developing system as a distributed network across tissues. We profiled nine tissues combining single-cell RNA sequencing, antigen-receptor and spatial transcriptomics to reconstruct system. This revealed late acquisition immune-effector functions by myeloid lymphoid subsets maturation monocytes T cells before peripheral tissue seeding. Moreover, we uncovered system-wide blood development beyond primary hematopoietic organs, characterized B1 cells, shed light on origin unconventional cells. Our atlas provides both valuable data resources biological insights that will facilitate engineering, regenerative medicine, disease understanding.

Language: Английский

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Screening cell–cell communication in spatial transcriptomics via collective optimal transport

Nature Methods, Journal Year: 2023, Volume and Issue: 20(2), P. 218 - 228

Published: Jan. 23, 2023

Abstract Spatial transcriptomic technologies and spatially annotated single-cell RNA sequencing datasets provide unprecedented opportunities to dissect cell–cell communication (CCC). However, incorporation of the spatial information complex biochemical processes required in reconstruction CCC remains a major challenge. Here, we present COMMOT (COMMunication analysis by Optimal Transport) infer transcriptomics, which accounts for competition between different ligand receptor species as well distances cells. A collective optimal transport method is developed handle molecular interactions constraints. Furthermore, introduce downstream tools signaling directionality genes regulated using machine learning models. We apply simulation data eight acquired with five show its effectiveness robustness identifying varying resolutions gene coverages. Finally, identifies new CCCs during skin morphogenesis case study human epidermal development.

Language: Английский

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Advances in spatial transcriptomic data analysis

Genome Research, Journal Year: 2021, Volume and Issue: 31(10), P. 1706 - 1718

Published: Oct. 1, 2021

Spatial transcriptomics is a rapidly growing field that promises to comprehensively characterize tissue organization and architecture at the single-cell or subcellular resolution. Such information provides solid foundation for mechanistic understanding of many biological processes in both health disease cannot be obtained by using traditional technologies. The development computational methods plays important roles extracting signals from raw data. Various approaches have been developed overcome technology-specific limitations such as spatial resolution, gene coverage, sensitivity, technical biases. Downstream analysis tools formulate cell–cell communications quantifiable properties, provide algorithms derive properties. Integrative pipelines further assemble multiple one package, allowing biologists conveniently analyze data beginning end. In this review, we summarize state art transcriptomic pipelines, discuss how they operate on different technological platforms.

Language: Английский

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Spatially resolved multiomics of human cardiac niches

Nature, Journal Year: 2023, Volume and Issue: 619(7971), P. 801 - 810

Published: July 12, 2023

The function of a cell is defined by its intrinsic characteristics and niche: the tissue microenvironment in which it dwells. Here we combine single-cell spatial transcriptomics data to discover cellular niches within eight regions human heart. We map cells microanatomical locations integrate knowledge-based unsupervised structural annotations. also profile cardiac conduction system

Language: Английский

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Impact of the Human Cell Atlas on medicine

Nature Medicine, Journal Year: 2022, Volume and Issue: 28(12), P. 2486 - 2496

Published: Dec. 1, 2022

Language: Английский

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Spatial multiomics map of trophoblast development in early pregnancy

Nature, Journal Year: 2023, Volume and Issue: 616(7955), P. 143 - 151

Published: March 29, 2023

Abstract The relationship between the human placenta—the extraembryonic organ made by fetus, and decidua—the mucosal layer of uterus, is essential to nurture protect fetus during pregnancy. Extravillous trophoblast cells (EVTs) derived from placental villi infiltrate decidua, transforming maternal arteries into high-conductance vessels 1 . Defects in invasion arterial transformation established early pregnancy underlie common disorders such as pre-eclampsia 2 Here we have generated a spatially resolved multiomics single-cell atlas entire maternal–fetal interface including myometrium, which enables us resolve full trajectory differentiation. We used this cellular map infer possible transcription factors mediating EVT show that they are preserved vitro models differentiation primary organoids 3,4 stem 5 define transcriptomes final cell states invasion: bed giant (fused multinucleated EVTs) endovascular EVTs (which form plugs inside arteries). predict cell–cell communication events contributing formation, model dual role interstitial Together, our data provide comprehensive analysis postimplantation can be inform design experimental placenta

Language: Английский

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