St2cell: Reconstruction of in situ single-cell spatial transcriptomics by integrating high-resolution histological image.

Spatially resolved transcriptomics (SRT) has greatly expanded our understanding of the spatial patterns of gene expression in histological tissue sections. However, most currently available platforms could not provide in situ single-cell spatial transcriptomics, limiting their biological applications. Here, to in silico reconstruct SRT at the single-cell resolution, we propose St2cell which combines deep learning-based frameworks with a novel convex quadratic programming (CQP)-based model. St2cell can thoroughly leverage information in high-resolution (HR) histological images, enabling the accurate segmentation of in situ single cells and identification of their transcriptomics. Applying St2cell on various SRT datasets, we demonstrated the reliability of reconstructed transcriptomics. The single-cell resolution provided by our proposed method greatly promoted the detection of elaborate spatial architectures and further facilitated the integration with single-cell RNA-sequencing data. Moreover, in a breast cancer tissue, St2cell identified general spatial structures and co-occurrence patterns of cell types in the tumor microenvironment. St2cell is also computationally efficient and easily accessible, making it a promising tool for SRT studies.