Towards Mapping Mouse Metabolic Tissue Atlas by Mid‐Infrared Imaging with Heavy Water Labeling

Abstract

Understanding metabolism is of great significance to decipher various physiological and pathogenic processes. While great progress has been made to profile gene expression, how to capture organ-, tissue-, and cell-type-specific metabolic profile (i.e., metabolic tissue atlas) in complex mammalian systems is lagging behind, largely owing to the lack of metabolic imaging tools with high resolution and high throughput. Here, the authors applied mid-infrared imaging coupled with heavy water (D 2 O) metabolic labeling to a scope of mouse organs and tissues. The premise is that, as D 2 O participates in the biosynthesis of various macromolecules, the resulting broad C-D vibrational spectrum should interrogate a wide range of metabolic pathways. Applying multivariate analysis to the C-D spectrum, the authors successfully identified both inter-organ and intra-tissue metabolic signatures of mice. A large-scale metabolic atlas map between different organs from the same mice is thus generated. Moreover, leveraging the power of unsupervised clustering methods, spatially-resolved metabolic signatures of brain tissues are discovered, revealing tissue and cell-type specific metabolic profile in situ. As a demonstration of this technique, the authors captured metabolic changes during brain development and characterized intratumoral metabolic heterogeneity of glioblastoma. Altogether, the integrated platform paves a way to map the metabolic tissue atlas for complex mammalian systems.

Two-color infrared photothermal microscopy

“…Extensive efforts were made to visualize a specific metabolic process by introducing a site-specifically labeled IR probe. 37,38 Many IR probes, e.g. , asymmetric azido stretch mode of N 3 -derivatized biomolecules and deuterated molecules with C–D bonds, have been used in various vibrational spectroscopic studies of biomolecules because their IR absorption bands are in the transparent and cell-silent IR spectral window (from 1800 to 2700 cm −1 ).…”

“…Extensive efforts were made to visualize a specific metabolic process by introducing a site-specifically labeled IR probe. 37,38 Many IR probes, e.g., asymmetric azido stretch mode of N 3 -derivatized biomolecules and deuterated molecules with C-D bonds, have been used in various vibrational spectroscopic studies of biomolecules because their IR absorption bands are in the transparent and cell-silent IR spectral window (from 1800 to 2700 cm −1 ). [39][40][41][42] Note that such small IR probes are highly sensitive to local electrostatic and hydration environments and are substantially more photochemically stable and biocompatible than relatively bulky fluorescent probes.…”

Single-cell mapping of lipid metabolites using an infrared probe in human-derived model systems

“…Infrared (IR) absorption provides over eight orders of magnitude stronger absorption cross sections when compared with Raman scattering 35 , which promises higher sensitivity and speed. While there are a handful of reports integrating different IR probes to study metabolism using Fourier transform IR or discrete frequency IR 29 , 36 , the coarse resolution associated with these IR imaging modalities presents challenges to achieving single-cell or even sub-cellular metabolic analysis and co-registration of other imaging modalities such as fluorescence imaging.…”

Solvent-induced luminescence behavior of Ce/Eu@Gd-MOF for ratiometric detection of D2O in H2O

“…[14][15][16] It possesses irreplaceable application value in chemical analysis, nuclear energy production, spectroscopic characterization and bioanalysis. [17][18][19] The similarity in the physical and chemical properties renders D 2 O and H 2 O highly suitable candidates for exploring solvent-induced luminescence behavior, minimizing the influence of factors such as solvent viscosity, chemical reactivity, and dispersibility. [20][21][22] From another perspective, the investigation of the luminescence behavior of Ln-MOFs in H 2 O and D 2 O also presents an opportunity to provide a rapid and convenient approach for detecting D 2 O content in H 2 O.…”