Di, W. | bioRxiv Science

bioRxiv2020

Bright Near-infrared Anti-Stokes Fluorescence of ICG under Low Power CW Laser Excitation and its Applications in Bioimaging

Anti-Stokes fluorescence was observed in ICG, a molecule approved by the FDA for clinical use. The wavelengths of its fluorescence are mainly located in the near-infrared band of 800 nm~900 nm, with a high quantum yield up to 8%. In order to know its generation mechanism, based on multi-photon absorption (MPA) theory, thermally activated delayed fluorescence (TADF) theory and hot band absorption theory, its power dependence, temperature dependence of absorption spectra and fluorescence spectra, and fluorescence lifetime were measured. Its generation mechanism was finally determined to be hot band absorption process. Since ICG showed bright anti-Stokes fluorescence in near-infrared region, which offers substantially longer penetration depth in biological tissues than visible light, excellent photostability and biosafety, we applied it to in vivo imaging and compared it with upconversion nanoparticles (UCNPs). The result is that ICG exhibited much stronger fluorescence than UCNPs, providing more anatomical information of samples. This contributes to a better choice for anti-Stokes fluorescence bioimaging.Competing Interest StatementThe authors have declared no competing interest.View Full Text

bioengineering↗

bioRxiv2020

ERG orchestrates chromatin interactions to drive prostate cell fate reprogramming

While cancer is commonly perceived as a disease of dedifferentiation, the hallmark of early stage prostate cancer is paradoxically the loss of more plastic basal cells and the abnormal proliferation of more differentiated secretory luminal cells. However, the mechanism of prostate cancer pro-luminal differentiation is largely unknown. Through integrating analysis of the transcription factors (TFs) from 806 human prostate cancers, we have identified that ERG highly correlated with prostate cancer luminal subtyping. ERG overexpression in luminal epithelial cells inhibits its normal plasticity to transdifferentiate into basal lineage and ERG supersedes PTEN-loss which favors basal differentiation. ERG knock-out disrupted prostate cell luminal differentiation, whereas AR knock-out had no such effects. Trp63 is a known master regulator of prostate basal lineage. Through analysis of 3D chromatin architecture, we found that ERG binds and inhibits the enhancer activity and chromatin looping of a Trp63 distal enhancer, thereby silencing its gene expression. Specific deletion of the distal ERG binding site resulted in the loss of ERG-mediated inhibition of basal differentiation. Thus, ERG orchestrates chromatin interactions and regulates prostate cell lineage toward pro-luminal program, as its fundamental role on lineage differentiation in prostate cancer initiation.

cancer biology↗