A better understanding of the cellular and molecular mechanisms involved in the reprogramming of somatic cells is essential for further improvement of induced pluripotent stem (iPS) cell technology. In this study, we enriched for cells actively undergoing reprogramming at different time points by sorting the cells stained with a stem cell-selective fluorescent chemical probe CDy1 for their global gene expression analysis. Day-to-day comparison of differentially expressed genes showed highly dynamic and transient gene expressions during reprogramming, which were largely distinct from those of fully-reprogrammed cells. An unbiased analysis of functional regulation indicated robust modulation of concurrent programs at critical junctures. Globally, transcriptional programs involved in cell proliferation, morphology and signal transduction were instantly triggered as early as 3 days-post-infection to prepare the cell for reprogramming but became somewhat muted in the final iPS cells. On the other hand, the highly coordinated metabolic reprogramming process was more gradually activated. Subsequent network analysis of differentially expressed genes indicated PDGF-BB as a core player in reprogramming which was verified by our gain- and loss-of-function experiments. As such, our study has revealed previously-unknown insights into the mechanisms of cellular reprogramming.
A quantitative structure‐fluorescence property relationship (QSPR) analysis of a large 288‐membered library based on a single fluorescent BODIPY scaffold is presented for the first time. BODIPY is a versatile fluorescent scaffold with outstanding photophysical properties. Absorption (λabs) and fluorescence emission (λem) wavelength maxima were modeled with help of stepwise multiple linear regression (MLR) and support vector regression (SVR). The models were rigorously validated by 10‐times 10‐fold cross‐validation (CV), y‐scrambling CV and with an external validation set. Non‐linear SVR models (R2=0.92 and Q2=0.71 for λabs; R2=0.89 and Q2=0.69 for λem) performed significantly better than linear models. A small root mean squared error (RMSE) of 5.62 nm and 11.07 nm was achieved for λabs and λem, respectively, and confirmed by external validation. A novel intramolecular charge transfer descriptor was developed based on the QSPR analysis and its inclusion in the modeling significantly improved models of λem. We conclude that QSPR is a useful tool for modeling λabs and λem of BODIPY fluorophores and suggest QSPR as an ideal partner for the design of compounds with tailored fluorescence properties in a diversity‐oriented fluorescence library approach (DOFLA).
The colorimetric response patterns of pH indicators and boronic acids ensemble array were used to analyze serial concentrations of mono-, disaccharides quantitatively. Furthermore, this ensemble array was successfully applied to quantify the sugar content in clinically used saline solutions.
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