scRICA-seq – simultaneous profiling of RNA isoforms and chromatin accessibility of single cells


Researchers at Sun Yat-Sen University have made an exciting breakthrough in understanding how neurons develop, particularly in the retina, by creating a new method called scRICA-seq. This method allows scientists to study two critical aspects of gene expression—RNA alternative splicing and chromatin accessibility—in individual cells at the same time. In simpler terms, scRICA-seq can show both how genes are activated and how they are read differently in each cell, which plays a vital role in how neurons form and grow.
Before scRICA-seq, methods couldn’t provide such a detailed look at these processes simultaneously. What makes this technique stand out is that it’s both highly sensitive and cost-effective, allowing the analysis of up to 10,000 cells in one experiment. The researchers applied this method to study human retinal organoids—miniature, lab-grown versions of the retina. This helped them create a detailed map of how retinal cells develop, revealing how specific genetic factors influence their fate.
Overview of scRICA-seq in high throughput

a Schematic illustration of scRICA-seq to simultaneously profile the RNA isoforms and chromatin accessibility for the same single nucleus, by integrating the scRNA-seq, scATAC-seq, scRCAT-seq2. b Schematic illustration of scRCAT-seq2 to depict the step-by-step procedure for generating the full-length cDNA library. CB: Cell barcode; UMI: Unique molecular identifier; TSO: Template-switching oligo; T30: 30 repeating T bases.
By linking changes in gene activation with different forms of RNA splicing, the team gained a deeper understanding of how neurons in the retina develop and determine their function. This approach could pave the way for advances in regenerative medicine, potentially aiding treatments for retinal diseases or injuries.
In summary, scRICA-seq opens up new avenues for exploring complex biological processes, providing a powerful tool for studying how neurons develop and regenerate. It represents a significant step toward unlocking the mysteries of neuronal development in the retina and beyond.

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