Metabolic Imaging at the Single-Cell Scale: Recent Advances in Mass Spectrometry Imaging

2019 ◽  
Vol 12 (1) ◽  
pp. 201-224 ◽  
Author(s):  
Ian S. Gilmore ◽  
Sven Heiles ◽  
Cornelius L. Pieterse

There is an increasing appreciation that every cell, even of the same type, is different. This complexity, when additionally combined with the variety of different cell types in tissue, is driving the need for spatially resolved omics at the single-cell scale. Rapid advances are being made in genomics and transcriptomics, but progress in metabolomics lags. This is partly because amplification and tagging strategies are not suited to dynamically created metabolite molecules. Mass spectrometry imaging has excellent potential for metabolic imaging. This review summarizes the recent advances in two of these techniques: matrix-assisted laser desorption ionization (MALDI) and secondary ion mass spectrometry (SIMS) and their convergence in subcellular spatial resolution and molecular information. The barriers that have held back progress such as lack of sensitivity and the breakthroughs that have been made including laser-postionization are highlighted as well as the future challenges and opportunities for metabolic imaging at the single-cell scale.

2011 ◽  
Vol 8 (5) ◽  
pp. 591-604 ◽  
Author(s):  
Kristin J Boggio ◽  
Emmanuel Obasuyi ◽  
Ken Sugino ◽  
Sacha B Nelson ◽  
Nathalie YR Agar ◽  
...  

2012 ◽  
Vol 84 (2) ◽  
pp. 893-900 ◽  
Author(s):  
Christopher A. Barnes ◽  
Jeremy Brison ◽  
Michael Robinson ◽  
Daniel J. Graham ◽  
David G. Castner ◽  
...  

2021 ◽  
Vol 7 (10) ◽  
pp. eabc5464
Author(s):  
Kiya W. Govek ◽  
Emma C. Troisi ◽  
Zhen Miao ◽  
Rachael G. Aubin ◽  
Steven Woodhouse ◽  
...  

Highly multiplexed immunohistochemistry (mIHC) enables the staining and quantification of dozens of antigens in a tissue section with single-cell resolution. However, annotating cell populations that differ little in the profiled antigens or for which the antibody panel does not include specific markers is challenging. To overcome this obstacle, we have developed an approach for enriching mIHC images with single-cell RNA sequencing data, building upon recent experimental procedures for augmenting single-cell transcriptomes with concurrent antigen measurements. Spatially-resolved Transcriptomics via Epitope Anchoring (STvEA) performs transcriptome-guided annotation of highly multiplexed cytometry datasets. It increases the level of detail in histological analyses by enabling the systematic annotation of nuanced cell populations, spatial patterns of transcription, and interactions between cell types. We demonstrate the utility of STvEA by uncovering the architecture of poorly characterized cell types in the murine spleen using published cytometry and mIHC data of this organ.


2021 ◽  
Vol 93 (10) ◽  
pp. 4463-4471
Author(s):  
Caroline Bouvier ◽  
Helen Glanville ◽  
Laurence de Viguerie ◽  
Chiara Merucci ◽  
Philippe Walter ◽  
...  

2020 ◽  
Author(s):  
Kimberly A. Aldinger ◽  
Zach Thomson ◽  
Parthiv Haldipur ◽  
Mei Deng ◽  
Andrew E. Timms ◽  
...  

ABSTRACTCerebellar development and function require precise regulation of molecular and cellular programs to coordinate motor functions and integrate network signals required for cognition and emotional regulation. However, molecular understanding of human cerebellar development is limited. Here, we combined spatially resolved and single-cell transcriptomics to systematically map the molecular, cellular, and spatial composition of early and mid-gestational human cerebellum. This enabled us to transcriptionally profile major cell types and examine the dynamics of gene expression within cell types and lineages across development. The resulting ‘Developmental Cell Atlas of the Human Cerebellum’ demonstrates that the molecular organization of the cerebellar anlage reflects cytoarchitecturally distinct regions and developmentally transient cell types that are insufficiently captured in bulk transcriptional profiles. By mapping disease genes onto cell types, we implicate the dysregulation of specific cerebellar cell types, especially Purkinje cells, in pediatric and adult neurological disorders. These data provide a critical resource for understanding human cerebellar development with implications for the cellular basis of cerebellar diseases.


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