Method of the Year: spatially resolved transcriptomics

Marx, Vivien

doi:10.1038/s41592-020-01033-y

Cited by 621 publications

(455 citation statements)

References 10 publications

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“…This limitation has implications both for differential gene expression, but also downstream deconvolution and indeed, the use of single-nucleus RNA-sequencing as a reference was found to decrease the performance of three deconvolution algorithms (including Scaden) on post-mortem human brain data [43]. This limitation stresses the importance of relating cell types defined by single-nucleus RNA-sequencing back to their spatial phenotypes, a process for which the emerging field of spatial transcriptomics will be instrumental in resolving [76]. Our results provide clear hypotheses to test using spatial transcriptomics both for cell-type-specific DE analysis and analysis of differential cell-type proportions.…”

Section: Discussionmentioning

confidence: 99%

Cross-platform transcriptional profiling identifies common and distinct molecular pathologies in Lewy Body diseases

Feleke

Reynolds

Smith

et al. 2021

Preprint

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Parkinson's disease (PD), Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB) are three clinically, genetically and neuropathologically overlapping neurodegenerative diseases collectively known as the Lewy body diseases (LBDs). A variety of molecular mechanisms have been implicated in PD pathogenesis, but the mechanisms underlying PDD and DLB remain largely unknown, a knowledge gap that presents an impediment to the discovery of disease-modifying therapies. Transcriptomic profiling can contribute to addressing this gap, but remains limited in the LBDs. Here, we applied paired bulk-tissue and single-nucleus RNA-sequencing to anterior cingulate cortex samples derived from 28 individuals, including healthy controls, PD, PDD and DLB cases (n = 7 per group), to transcriptomically profile the LBDs. Using this approach, we (i) found transcriptional alterations in multiple cell types across the LBDs; (ii) discovered evidence for widespread dysregulation of RNA splicing, particularly in PDD and DLB; (iii) identified potential splicing factors, with links to other dementia-related neurodegenerative diseases, coordinating this dysregulation; and (iv) identified transcriptomic commonalities and distinctions between the LBDs that inform understanding of the relationships between these three clinical disorders. Together, these findings have important implications for the design of RNA-targeted therapies for these diseases and highlight a potential molecular “window” of therapeutic opportunity between the initial onset of PD and subsequent development of Lewy body dementia.

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Section: Discussionmentioning

confidence: 99%

Cross-platform transcriptional profiling identifies common and distinct molecular pathologies in Lewy Body diseases

Feleke

Reynolds

Smith

et al. 2021

Preprint

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“…Recent studies examining the CMZ in unconventional species, including reptiles, have started to frame new questions on the conservation or lack thereof of the CMZ or CMZ-like niche and could inform on commonalities required for an active CMZ. Moreover, with the advancement of single-cell RNA sequencing [ 142 , 143 ] and spatial transcriptomics [ 144 ], it is now possible to obtain the transcriptome of cells found at the periphery of the retina in multiple different species and search for similarities in their gene expression profiles. Not only could this potentially identify with greater accuracy cells that exhibit similar stem cell characteristics across species and their location in the retina, but it may also identify novel mechanisms through which these cells are differentially regulated.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Retinal Stem Cell ‘Retirement Plans’: Growth, Regulation and Species Adaptations in the Retinal Ciliary Marginal Zone

Miles

Tropepe

2021

IJMS

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The vertebrate retina develops from a specified group of precursor cells that adopt distinct identities and generate lineages of either the neural retina, retinal pigmented epithelium, or ciliary body. In some species, including teleost fish and amphibians, proliferative cells with stem-cell-like properties capable of continuously supplying new retinal cells post-embryonically have been characterized and extensively studied. This region, termed the ciliary or circumferential marginal zone (CMZ), possibly represents a conserved retinal stem cell niche. In this review, we highlight the research characterizing similar CMZ-like regions, or stem-like cells located at the peripheral margin, across multiple different species. We discuss the proliferative parameters, multipotency and growth mechanisms of these cells to understand how they behave in vivo and how different molecular factors and signalling networks converge at the CMZ niche to regulate their activity. The evidence suggests that the mature retina may have a conserved propensity for homeostatic growth and plasticity and that dysfunction in the regulation of CMZ activity may partially account for dystrophic eye growth diseases such as myopia and hyperopia. A better understanding of the properties of CMZ cells will enable important insight into how an endogenous generative tissue compartment can adapt to altered retinal physiology and potentially even restore vision loss caused by retinal degenerative conditions.

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“…It is clear that OC can obtain resistance through a range of pathways, many of which are linked to oncogenic kinase signaling [102]. Recent advances in single-cell technologies such as spatial profiling [103] and single-cell proteomics [104] have great potential for uncovering tumor heterogeneity and shedding light on mechanisms for inherent and acquired drug resistance. Mechanisms underlying drug resistance can be delineated using preclinical OC cell line models [105,106].…”

Section: Ovarian Cancer Drug Resistance and Proteomicsmentioning

confidence: 99%

Comprehending the Proteomic Landscape of Ovarian Cancer: A Road to the Discovery of Disease Biomarkers

et al. 2021

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Despite recent technological advancements allowing the characterization of cancers at a molecular level along with biomarkers for cancer diagnosis, the management of ovarian cancers (OC) remains challenging. Proteins assume functions encoded by the genome and the complete set of proteins, termed the proteome, reflects the health state. Comprehending the circulatory proteomic profiles for OC subtypes, therefore, has the potential to reveal biomarkers with clinical utility concerning early diagnosis or to predict response to specific therapies. Furthermore, characterization of the proteomic landscape of tumor-derived tissue, cell lines, and PDX models has led to the molecular stratification of patient groups, with implications for personalized therapy and management of drug resistance. Here, we review single and multiple marker panels that have been identified through proteomic investigations of patient sera, effusions, and other biospecimens. We discuss their clinical utility and implementation into clinical practice.

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Method of the Year: spatially resolved transcriptomics

Cited by 621 publications

References 10 publications

Cross-platform transcriptional profiling identifies common and distinct molecular pathologies in Lewy Body diseases

Cross-platform transcriptional profiling identifies common and distinct molecular pathologies in Lewy Body diseases

Retinal Stem Cell ‘Retirement Plans’: Growth, Regulation and Species Adaptations in the Retinal Ciliary Marginal Zone

Comprehending the Proteomic Landscape of Ovarian Cancer: A Road to the Discovery of Disease Biomarkers

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