Integration of whole transcriptome spatial profiling with protein markers

Ben-Chetrit, Nir; Niu, Xiang; Swett, Ariel D; Sotélo, Jesús Alfonso López; Jiao, Maria S.; Stewart, Caitlin M.; Potenski, Catherine; Mielinis, Paulius; Roelli, Patrick; Stoeckius, Marlon; Landau, Dan A.

doi:10.1038/s41587-022-01536-3

Cited by 82 publications

(82 citation statements)

References 48 publications

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“…This was applied to P22 mouse brain coronal sections (at bregma 1) for joint profiling of chromatin accessibility with transcriptome. In contrast to E13 mouse embryonic brain, we found a higher number of ATAC clusters ( 14) compared with RNA clusters (11), indicating terminal differentiation of most major cell types in the juvenile brain relative to that in embryo, which consists of many undifferentiated or multipotent cell states. Spatial distribution of clusters agreed with the anatomical annotation defined by Nissl staining, reflecting arealization of the juvenile brain (Fig.…”

Section: Spatial Atac-rna-seq Of Mouse Braincontrasting

confidence: 65%

Spatial epigenome–transcriptome co-profiling of mammalian tissues

Zhang

Deng

Kukanja

et al. 2023

Nature

156

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Emerging spatial technologies, including spatial transcriptomics and spatial epigenomics, are becoming powerful tools for profiling of cellular states in the tissue context1–5. However, current methods capture only one layer of omics information at a time, precluding the possibility of examining the mechanistic relationship across the central dogma of molecular biology. Here, we present two technologies for spatially resolved, genome-wide, joint profiling of the epigenome and transcriptome by cosequencing chromatin accessibility and gene expression, or histone modifications (H3K27me3, H3K27ac or H3K4me3) and gene expression on the same tissue section at near-single-cell resolution. These were applied to embryonic and juvenile mouse brain, as well as adult human brain, to map how epigenetic mechanisms control transcriptional phenotype and cell dynamics in tissue. Although highly concordant tissue features were identified by either spatial epigenome or spatial transcriptome we also observed distinct patterns, suggesting their differential roles in defining cell states. Linking epigenome to transcriptome pixel by pixel allows the uncovering of new insights in spatial epigenetic priming, differentiation and gene regulation within the tissue architecture. These technologies are of great interest in life science and biomedical research.

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Section: Spatial Atac-rna-seq Of Mouse Braincontrasting

confidence: 65%

Spatial epigenome–transcriptome co-profiling of mammalian tissues

Zhang

Deng

Kukanja

et al. 2023

Nature

156

View full text Add to dashboard Cite

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“…This design will facilitate the use and integration of additional data types. For example, emerging spatial profiling technologies have been proposed to study epigenetic cell features 51 , copy number alterations 52 , chromatin accessibility 53 , and combined single-cell RNA-seq and protein profiles 17,54,55 . In addition, all these molecular layers could be combined with cell morphology and tissue architectural features derived from hematoxylin and eosin (H&E) staining.…”

Section: Discussionmentioning

confidence: 99%

CellCharter reveals spatial cell niches associated with tissue remodeling and cell plasticity

Varrone

Tavernari

Santamaria-Martínez

et al. 2023

Preprint

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Tissues are organized in niches where cell types interact to implement specific functions. Spatial -omics technologies allow to decode the molecular features and spatial interactions that determine such niches. However, computational approaches to process and interpret spatial molecular profiles are challenged by the scale and diversity of this data. Here, we present CellCharter, an algorithmic framework for the identification, characterization, and comparison of cellular niches from heterogeneous spatial transcriptomics and proteomics datasets comprising multiple samples. CellCharter outperformed existing methods, identified biologically meaningful cellular niches in different contexts, and discovered spatial cancer cell states, characterized by cell-intrinsic features and spatial interactions between tumor and immune cells. In non-small cell lung cancer, CellCharter revealed a cellular niche composed of neutrophils and tumor cells expressing markers of hypoxia and cell migration. Expression of these markers determined a spatial gradient associated with cancer cell state transition and neutrophil infiltration. Moreover, CellCharter showed that similar compositions of immune cell types can exhibit remarkably different spatial organizations in different tumors, highlighting the need for exploring spatial cell interactions to decipher intratumor heterogeneity. Overall, CellCharter is a flexible and scalable framework to explore and compare the spatial organization of normal and malignant tissues.

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“…Array-based spatial transcriptome was also expanded to multi-omics, namely SM-Omics 7 , which demonstrated the mapping of six proteins and whole transcriptome with 100-µm spot size. Very recently, Landau et al 8 further implemented spatial multi-omics on the 10x Visium platform with 55-µm spot size and a panel of 21 protein markers. Spatial proteogenomic profiling of liver tissue demonstrated highly multiplexed (~100) protein measurement using Visium 9 .…”

mentioning

confidence: 99%

High-plex protein and whole transcriptome co-mapping at cellular resolution with spatial CITE-seq

et al. 2023

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In this study, we extended co-indexing of transcriptomes and epitopes (CITE) to the spatial dimension and demonstrated high-plex protein and whole transcriptome co-mapping. We profiled 189 proteins and whole transcriptome in multiple mouse tissue types with spatial CITE sequencing and then further applied the method to measure 273 proteins and transcriptome in human tissues, revealing spatially distinct germinal center reactions in tonsil and early immune activation in skin at the Coronavirus Disease 2019 mRNA vaccine injection site.

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Integration of whole transcriptome spatial profiling with protein markers

Cited by 82 publications

References 48 publications

Spatial epigenome–transcriptome co-profiling of mammalian tissues

Spatial epigenome–transcriptome co-profiling of mammalian tissues

CellCharter reveals spatial cell niches associated with tissue remodeling and cell plasticity

High-plex protein and whole transcriptome co-mapping at cellular resolution with spatial CITE-seq

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