BACKGROUND: The heterogeneity of tumors significantly impacts on colorectal cancer (CRC) progression. However, the influence of this heterogeneity on the spatial architecture of CRC remains largely unknown. METHODS: Spatial transcriptomic (ST) analysis of AOM/DSS-induced colorectal cancer (CRC), integrated with single-cell RNA sequencing, generated a comprehensive spatial atlas of CRC. Pseudotime trajectory, stemness evaluation, and cell-cell communication analyses explored how CD44 RESULTS: Our findings revealed a distinctive layered ring-like structure within CRC tissues, where CD44 CONCLUSIONS: Our results provide distinctive insights into how tumor heterogeneity reshapes the TME at the leading edge of tumor, thereby promoting CRC progression.