Following Embryonic Stem Cells, Their Differentiated Progeny, and Cell-State Changes During iPS Reprogramming by Raman Spectroscopy

Monitoring
cell-state transition in pluripotent cells is invaluable
for application and basic research. In this study, we demonstrate
the pertinence of noninvasive, label-free Raman spectroscopy to monitor
and characterize the cell-state transition of mouse stem cells undergoing
reprogramming. Using an isogenic cell line of mouse stem cells, reprogramming
from neuronal cells was performed, and we showcase a comparative analysis
of living single-cell spectral data of the original stem cells, their
neuronal progenitors, and reprogrammed cells. Neural network, regression
models, and ratiometric analyses were used to discriminate the cell
states and extract several important biomarkers specific to differentiation
or reprogramming. Our results indicated that the Raman spectrum allowed
us to build a low-dimensional space allowing us to monitor and characterize
the dynamics of cell-state transition at a single-cell level, scattered
in heterogeneous populations. The ability of monitoring pluripotency
by Raman spectroscopy and distinguishing differences between ES and
reprogrammed cells is also discussed.