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Non-contact, Label-free Monitoring of Cells and Extracellular Matrix using Raman Spectroscopy
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RamanOmics Decodes Spatial Vibrational-Molecular Architecture and Rewiring in Aging and Repair.

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We developed RamanOmics, a new method combining Raman imaging and sequencing, to map aging and tissue repair. This approach reveals tissue-specific cellular changes and identifies a conserved biochemical signature for senescent cells.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Genomics
  • Biophysics

Background:

  • Aging and tissue repair involve complex, spatially varied remodeling across molecular and cellular levels.
  • Current definitions of aging and senescence often use isolated markers, missing the co-evolution of biochemical and transcriptional states.
  • Understanding these integrated states is crucial for deciphering tissue aging and repair mechanisms.

Purpose of the Study:

  • To present RamanOmics, a multimodal framework integrating Raman imaging with single-nucleus RNA sequencing and spatial transcriptomics.
  • To map the spatial biochemical and molecular architecture of aging and senescence in intact tissues.
  • To develop a method for non-destructive, in situ identification and characterization of senescent cells.

Main Methods:

  • Integration of label-free Raman imaging with single-nucleus RNA sequencing (snRNA-seq) and spatial transcriptomics.
  • Application of the RamanOmics framework to mouse lung and skin tissues.
  • Development of a machine learning-based multimodal barcode to quantitatively integrate biochemical and transcriptional data.

Main Results:

  • RamanOmics generated spatially resolved biochemical-molecular maps of aging and senescence.
  • Identified tissue-specific senescence programs in lung (ECM remodeling, TGF-β signaling) and skin (keratinization, barrier homeostasis).
  • Discovered a conserved branched-chain fatty-acid-linked biochemical profile and Raman signature marking senescent cells across tissues.
  • Demonstrated coordinated reactivation of barrier-repair programs in senescent cells during wound healing.

Conclusions:

  • RamanOmics provides a powerful framework for multimodal profiling of cellular states in aging and tissue repair.
  • The study reveals conserved and tissue-specific molecular and biochemical signatures of senescence.
  • This approach enables non-destructive, in situ identification of senescence and offers insights into dynamic tissue remodeling processes.