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Plate IV.214 · Publications

Spatial proteomics in three-dimensional intact specimens

Article in Cell, December 2022.

Spatial, Omics Data

  1. Harsharan Singh Bhatia
  2. Andreas-David Brunner
  3. Furkan Öztürk
  4. Saketh Kapoor
  5. Zhouyi Rong
  6. Hongcheng Mai
  7. Marvin Thielert
  8. Mayar Ali
  9. Rami Al-Maskari
  10. Johannes Christian Paetzold
  11. Florian Kofler
  12. Mihail Ivilinov Todorov
  13. Muge Molbay
  14. Zeynep Ilgin Kolabas
  15. Moritz Negwer
  16. Luciano Hoeher
  17. Hanno Steinke
  18. Alina Dima
  19. Basavdatta Gupta
  20. Doris Kaltenecker
  21. Özüm Sehnaz Caliskan
  22. Daniel Brandt
  23. Natalie Krahmer
  24. Stephan Müller
  25. Stefan Frieder Lichtenthaler
  26. Farida Hellal
  27. Ingo Bechmann
  28. Bjoern Menze
  29. Fabian Theis
  30. Matthias Mann
  31. Ali Ertürk

Abstract

Spatial molecular profiling of complex tissues is essential to investigate cellular function in physiological and pathological states. However, methods for molecular analysis of large biological specimens imaged in 3D are lacking. Here, we present DISCO-MS, a technology that combines whole-organ/whole-organism clearing and imaging, deep-learning-based image analysis, robotic tissue extraction, and ultra-high-sensitivity mass spectrometry. DISCO-MS yielded proteome data indistinguishable from uncleared samples in both rodent and human tissues. We used DISCO-MS to investigate microglia activation along axonal tracts after brain injury and characterized early- and late-stage individual amyloid-beta plaques in a mouse model of Alzheimer's disease. DISCO-bot robotic sample extraction enabled us to study the regional heterogeneity of immune cells in intact mouse bodies and aortic plaques in a complete human heart. DISCO-MS enables unbiased proteome analysis of preclinical and clinical tissues after unbiased imaging of entire specimens in 3D, identifying diagnostic and therapeutic opportunities for complex diseases. VIDEO ABSTRACT.

Cite

@article{bhatia2022spatial,
  title = {{Spatial proteomics in three-dimensional intact specimens}},
  author = {Bhatia, Harsharan Singh and Brunner, Andreas-David and Öztürk, Furkan and Kapoor, Saketh and Rong, Zhouyi and Mai, Hongcheng and Thielert, Marvin and Ali, Mayar and Al-Maskari, Rami and Paetzold, Johannes Christian and Kofler, Florian and Todorov, Mihail Ivilinov and Molbay, Muge and Kolabas, Zeynep Ilgin and Negwer, Moritz and Hoeher, Luciano and Steinke, Hanno and Dima, Alina and Gupta, Basavdatta and Kaltenecker, Doris and Caliskan, Özüm Sehnaz and Brandt, Daniel and Krahmer, Natalie and Müller, Stephan and Lichtenthaler, Stefan Frieder and Hellal, Farida and Bechmann, Ingo and Menze, Bjoern and Theis, Fabian and Mann, Matthias and Ertürk, Ali},
  journal = {Cell},
  publisher = {Elsevier BV},
  year = {2022},
  month = dec,
  doi = {10.1016/j.cell.2022.11.021},
  url = {https://doi.org/10.1016/j.cell.2022.11.021},
  pmid = {36563667}
}
.bib file