Fluctuation of Raman scattering can be an initial marker for iPSC differentiation

Abstract

Change in the intensity of Raman scattering peaks from living cells or tissues have been widely used to estimate the type or state of the specimen. Transition of cell state can also be estimated by Raman spectrum of the cells; however, subtle change such as initiation of differentiation is difficult to detect because of the low signal of the Raman scattering. In this study, we have successfully detected the onset of the iPSC differentiation by using the fluctuation of the Raman scattering peak intensities during cardiomyogenesis. To detect the fluctuation of the Raman peaks in non-labeling and non-destructive manner, we have developed a technique to collect Raman scattering spectra with high reproducibility, independent of experimental date, analyst, and optical aberrations. Using this newly developed method, small fluctuation in Raman peaks can be observed. Fluctuation in Raman peaks was observed earlier than the change in Raman peak intensities, showing that fluctuation-based analysis can be useful in detecting the onset of cell state transition. We also applied Dynamic Network Biomarker (DNB) based analysis to the obtained dataset, which also showed earlier detection of the onset of cell state transition, indicating that fluctuation-based analysis will be a strong tool in cell spectrum analysis.