Computer-aided design of reversible hybridization chain reaction (CAD-HCR) enables multiplexed single-cell spatial proteomics imaging

Cyclic imaging of multiple proteins in a single cell is realized through CAD-HCR.

A novel FRET-based dendritic hybridization chain reaction for tumour-related mRNA imaging

A novel FRET-based dendritic hybridization chain reaction (D-HCR) for TK1 mRNA imaging was developed in living cells. Compared to the traditional complex D-HCR methods, it has the following advantages, including...

Fast and specific enrichment of cancer-related exosomes by DNA-nanoweight-assisted centrifugation

Exosomes are nanoscale membrane vesicles actively released by cells and play an important role in the diagnosis of cancer-related diseases. However, it is challenging to efficiently enrich exosomes from extracellular fluids. In this work, we used DNA-tetrahedron as a nanoweight during centrifugation to precisely enrich tumor exosomes from a complex biological environment. Two different DNA tetrahedral nanostructures (DTAs), each carrying a specific aptamer for exosome biomarker recognition, were incubated with clinical samples simultaneously. One DTA triggered the cross-linking of multiple target exosomes, and therefore enabled low-speed and fast centrifugation for enrichment. The other DTA further narrowed down the target exosome subtype and initiated a hybridization chain reaction (HCR) for sensitive signal amplification. The method enabled the detection of 180 MCF-7-derived exosomes per microliter and 560 HepG2-derived exosomes per microliter, with 1000-fold higher sensitivity than conventional ELISA. This easy-to-operate method can enrich exosomes with excellent specificity and therefore will be appealing in biomedical research and clinical diagnosis.

Modulation of retinoid-X-receptors differentially regulates expression of apolipoprotein genes apoc1 and apoeb by zebrafish microglia

Transcriptome analyses performed in both human and zebrafish indicate strong expression of Apoe and Apoc1 by microglia. Apoe expression by microglia is well appreciated, but Apoc1 expression has not been well-examined. PPAR/RXR and LXR/RXR receptors appear to regulate expression of the apolipoprotein gene cluster in macrophages, but a similar role in microglia in vivo has not been studied. Here, we characterized microglial expression of apoc1 in the zebrafish central nervous system (CNS) in situ and demonstrate that in the CNS, apoc1 expression is unique to microglia. We then examined the effects of PPAR/RXR and LXR/RXR modulation on microglial expression of apoc1 and apoeb during early CNS development using a pharmacological approach. Changes in apoc1 and apoeb transcripts in response to pharmacological modulation were quantified by RT-qPCR in whole heads, and in individual microglia using hybridization chain reaction (HCR) in situ hybridization. We found that expression of apoc1 and apoeb by microglia were differentially regulated by LXR/RXR and PPAR/RXR modulating compounds, respectively, during development. Our results also suggest RXR receptors could be involved in endogenous induction of apoc1 expression by microglia. Collectively, our work supports the use of zebrafish to better understand regulation and function of these apolipoproteins in the CNS.