Cited by 470Advanced Fluorescence Microscopy TechniquesCell Image Analysis TechniquesOptical Imaging and Spectroscopy Techniques

Panoptic imaging of transparent mice reveals whole-body neuronal projections and skull–meninges connections

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Cai, Ruiyao, Pan, Chenchen, Ghasemigharagoz, Alireza, Todorov, Mihail Ivilinov, Förstera, Benjamin, Zhao, Shan, Bhatia, Harsharan S., Parra-Damas, Arnaldo +14 more·2019·Nature Neuroscience

Abstract

Analysis of entire transparent rodent bodies after clearing could provide holistic biological information in health and disease, but reliable imaging and quantification of fluorescent protein signals deep inside the tissues has remained a challenge. Here, we developed vDISCO, a pressure-driven, nanobody-based whole-body immunolabeling technology to enhance the signal of fluorescent proteins by up to two orders of magnitude. This allowed us to image and quantify subcellular details through bones, skin and highly autofluorescent tissues of intact transparent mice. For the first time, we visualized whole-body neuronal projections in adult mice. We assessed CNS trauma effects in the whole body and found degeneration of peripheral nerve terminals in the torso. Furthermore, vDISCO revealed short vascular connections between skull marrow and brain meninges, which were filled with immune cells upon stroke. Thus, our new approach enables unbiased comprehensive studies of the interactions between the nervous system and the rest of the body.

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Crossref · 10.1038/s41593-018-0301-3

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  • vDISCO with GFP-Nanobooster labelling amplifies the endogenous eGFP signal and shifts it into the far-red spectrum, substantially improving signal-to-noise ratios throughout the tissue.

    “This approach amplifies the endogenous eGFP signal in reporter mice and shifts it into the far-red spectrum, substantially improving signal-to-noise ratios throughout the tissue.”

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Authors
Cai, R., Pan, C., Ghasemigharagoz, A., Todorov, M. I., Förstera, B., Zhao, S., Bhatia, H. S., Parra-Damas, A., Mrowka, L., Theodorou, D., Rempfler, M., Xavier, A. L. R., Kress, B. T., Benakis, C., Steinke, H., Liebscher, S., Bechmann, I., Liesz, A., Menze, B., Kerschensteiner, M., Nedergaard, M., & Ertürk, A.
Affiliations
  • Institut für Schlaganfall- und Demenzforschung (DE)
  • Institut für Klinische Neuroimmunologie (DE)
  • Technical University of Munich (DE)
  • University of Copenhagen (DK)
  • Leipzig University (DE)
  • Munich Cluster for Systems Neurology (DE)
  • LMU Klinikum (DE)
Corresponding author
Ertürk, Ali
Venue
Nature Neuroscience
Published
2018-12-31
Volume
22
Issue
2
Pages
317-327
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
OpenAlex
W2906442564
Cited by
470
References
54
Citations by year
2026: 44 · 2025: 63 · 2024: 74 · 2023: 62 · 2022: 73 · 2021: 74 · 2020: 54 · 2019: 26
FWCI
19.92
Type
journal article
Language
en
Open access
Locations
  • Nature Neuroscience (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Deutsche Forschungsgemeinschaft
  • Fritz Thyssen Stiftung
  • Lundbeckfonden (R209-2015-2920, R155-2016–552)
  • Novo Nordisk
  • Novo Nordisk Fonden (NNF13OC0004258)
  • H. Lundbeck A/S
  • Stiftung zur Erforschung der Vaskulären Demenz
  • National Institutes of Health
  • National Institute on Aging (RF1AG057575, R01AG048769)
  • National Institute of Neurological Disorders and Stroke (RF1NS110049, R01NS100366)
  • Graduate School of Systemic Neurosciences
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Cell Image Analysis Techniques
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Optical Imaging and Spectroscopy Techniques
Keywords
whole-body imaging, tissue clearing, neuronal projections, cranial meninges, stroke, immune cells, peripheral nerve degeneration, CNS trauma
MeSH terms
Animals, Meninges, Mice, Transgenic, Neurons, Skull, Mice, Whole Body Imaging

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