Toward Gene-Correlated Spatially Resolved Metabolomics with Fingerprint Coherent Raman Imaging

Raman spectroscopy has long been known to provide sufficientinformationto discriminate distinct cell phenotypes. Underlying this discriminatingcapability is that Raman spectra provide an overall readout of themetabolic profiles that change with transcriptomic activity. Robustlyassociating Raman spectral changes with the regulation of specificsignaling pathways may be possible, but the spectral signals of interestmay be weak and vary somewhat among individuals. Establishing a Raman-to-transcriptomemapping will thus require tightly controlled and easily manipulatedbiological systems and high-throughput spectral acquisition. We attemptto meet these requirements using broadband coherent anti-Stokes Ramanscattering (BCARS) microscopy to spatio-spectrally map the C. elegans hermaphrodite gonad in vivo at subcellular resolution. The C. elegans hermaphrodite gonad is an ideal model system with a sequential,continuous process of highly regulated spatiotemporal cellular events.We demonstrate that the BCARS spatio-spectral signatures correlatewith gene expression profiles in the gonad, evincing that BCARS haspotential as a spatially resolved omics surrogate.