SpaceM reveals metabolic states of single cells

Rappez, Luca; Stadler, Mira; Triana, Sergio; Gathungu, Rose M.; Ovchinnikova, Katja; Phapale, Prasad; Heikenwälder, Mathias; Alexandrov, Theodore

doi:10.1038/s41592-021-01198-0

Cited by 225 publications

(210 citation statements)

References 59 publications

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“…Recently, an open-source single-cell metabolomics method named SpaceM, which integrates light microscopy and MALDI-MSI has been developed for in situ detection of >100 metabolites from >1,000 individual cells per hour together with a fluorescence-based read out and retention of morphological spatial features based on fluorescence (Rappez et al, 2021). In addition, SpaceM can easily distinguish between cells in a state.…”

Section: Single-cell Metabolomicsmentioning

confidence: 99%

Advances in MALDI Mass Spectrometry Imaging Single Cell and Tissues

Zhu

Chen

et al. 2022

Front. Chem.

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Compared with conventional optical microscopy techniques, mass spectrometry imaging (MSI) or imaging mass spectrometry (IMS) is a powerful, label-free analytical technique, which can sensitively and simultaneously detect, quantify, and map hundreds of biomolecules, such as peptides, proteins, lipid, and other organic compounds in cells and tissues. So far, although several soft ionization techniques, such as desorption electrospray ionization (DESI) and secondary ion mass spectrometry (SIMS) have been used for imaging biomolecules, matrix-assisted laser desorption/ionization (MALDI) is still the most widespread MSI scanning method. Here, we aim to provide a comprehensive review of MALDI-MSI with an emphasis on its advances of the instrumentation, methods, application, and future directions in single cell and biological tissues.

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Section: Single-cell Metabolomicsmentioning

confidence: 99%

Advances in MALDI Mass Spectrometry Imaging Single Cell and Tissues

Zhu

Chen

et al. 2022

Front. Chem.

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“…The current progress and challenges associated with single-cell proteomics or single-cell metabolomics have been outlined very recently [ 131 , 132 ]. It is worth highlighting that Rappez and colleagues applied their single-cell metabolomics technology SpaceM in an in vitro NAFL/NASH model and detected a steatosis-prone hepatocyte subpopulation (24% of all cells) in the milder NAFL setting, which expanded to 93% of all cells in an inflamed context mimicking NASH [ 133 ]. It will be exciting to investigate whether such hepatocyte subpopulation exists in vivo, representing a potential novel drug target for early disease reversal.…”

Section: Emerging Technologies To Analyze the Cis-regulatory Genome A...mentioning

confidence: 99%

Cell-Type Resolved Insights into the Cis-Regulatory Genome of NAFLD

Dam

Toft

Grøntved

2022

Cells

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The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing rapidly, and unmet treatment can result in the development of hepatitis, fibrosis, and liver failure. There are difficulties involved in diagnosing NAFLD early and for this reason there are challenges involved in its treatment. Furthermore, no drugs are currently approved to alleviate complications, a fact which highlights the need for further insight into disease mechanisms. NAFLD pathogenesis is associated with complex cellular changes, including hepatocyte steatosis, immune cell infiltration, endothelial dysfunction, hepatic stellate cell activation, and epithelial ductular reaction. Many of these cellular changes are controlled by dramatic changes in gene expression orchestrated by the cis-regulatory genome and associated transcription factors. Thus, to understand disease mechanisms, we need extensive insights into the gene regulatory mechanisms associated with tissue remodeling. Mapping cis-regulatory regions genome-wide is a step towards this objective and several current and emerging technologies allow detection of accessible chromatin and specific histone modifications in enriched cell populations of the liver, as well as in single cells. Here, we discuss recent insights into the cis-regulatory genome in NAFLD both at the organ-level and in specific cell populations of the liver. Moreover, we highlight emerging technologies that enable single-cell resolved analysis of the cis-regulatory genome of the liver.

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“…Recent work in neurodegeneration has harnessed single cell sequencing technologies to better reveal mitochondrial changes in disease states such as Parkinson’s Disease ( Bailey et al, 2021 ). Thoughtful employment of single cell sequencing, spatial and single cell metabolomics ( Rappez et al, 2021 ), and other new methods has the potential to drive the field forward to identify additional key mitochondrial roles in neurodevelopment and neurodevelopmental diseases.…”

Section: Implications and Open Questionsmentioning

confidence: 99%

Mitochondria in Early Forebrain Development: From Neurulation to Mid-Corticogenesis

Fame

Lehtinen

2021

Front. Cell Dev. Biol.

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Function of the mature central nervous system (CNS) requires a substantial proportion of the body’s energy consumption. During development, the CNS anlage must maintain its structure and perform stage-specific functions as it proceeds through discrete developmental stages. While key extrinsic signals and internal transcriptional controls over these processes are well appreciated, metabolic and mitochondrial states are also critical to appropriate forebrain development. Specifically, metabolic state, mitochondrial function, and mitochondrial dynamics/localization play critical roles in neurulation and CNS progenitor specification, progenitor proliferation and survival, neurogenesis, neural migration, and neurite outgrowth and synaptogenesis. With the goal of integrating neurodevelopmental biologists and mitochondrial specialists, this review synthesizes data from disparate models and processes to compile and highlight key roles of mitochondria in the early development of the CNS with specific focus on forebrain development and corticogenesis.

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SpaceM reveals metabolic states of single cells

Cited by 225 publications

References 59 publications

Advances in MALDI Mass Spectrometry Imaging Single Cell and Tissues

Advances in MALDI Mass Spectrometry Imaging Single Cell and Tissues

Cell-Type Resolved Insights into the Cis-Regulatory Genome of NAFLD

Mitochondria in Early Forebrain Development: From Neurulation to Mid-Corticogenesis

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