The paper introduces seqFISH+, a novel method for transcriptome-scale super-resolved imaging in tissues using RNA-seqFISH. This technique overcomes the limitations of optical resolution and transcript density in single cells by employing a large palette of "pseudocolors" to dilute mRNA molecules and achieve sub-diffraction-limit resolution. seqFISH+ can image 10,000 genes in single cells with high accuracy and multiplexing, using a standard confocal microscope. The method is demonstrated in mouse brain tissues, including the cortex, subventricular zone, and olfactory bulb, allowing for unbiased identification of cell classes and their spatial organization. seqFISH+ also reveals subcellular mRNA localization patterns and ligand-receptor pairs across neighboring cells, enabling the generation of spatial cell atlases and discovery-driven studies of biological processes in situ. The technology shows an 8-fold reduction in imaging time compared to existing methods and provides a 10-fold or more improvement in the number of mRNAs profiled and the total number of RNA barcodes detected per cell.The paper introduces seqFISH+, a novel method for transcriptome-scale super-resolved imaging in tissues using RNA-seqFISH. This technique overcomes the limitations of optical resolution and transcript density in single cells by employing a large palette of "pseudocolors" to dilute mRNA molecules and achieve sub-diffraction-limit resolution. seqFISH+ can image 10,000 genes in single cells with high accuracy and multiplexing, using a standard confocal microscope. The method is demonstrated in mouse brain tissues, including the cortex, subventricular zone, and olfactory bulb, allowing for unbiased identification of cell classes and their spatial organization. seqFISH+ also reveals subcellular mRNA localization patterns and ligand-receptor pairs across neighboring cells, enabling the generation of spatial cell atlases and discovery-driven studies of biological processes in situ. The technology shows an 8-fold reduction in imaging time compared to existing methods and provides a 10-fold or more improvement in the number of mRNAs profiled and the total number of RNA barcodes detected per cell.