CellNiche represents cellular microenvironments in atlas-scale spatial omics data with contrastive learning.

Deciphering cellular microenvironments at atlas scale remains challenging because molecular identity, spatial context, and platform heterogeneity are tightly coupled. Here we present CellNiche, a scalable contrastive-learning framework that identifies and characterizes cellular microenvironments from spatial omics data using cell-centric spatial-proximity subgraphs. CellNiche combines spatial co-localization and molecular co-expression cues to learn microenvironment-aware embeddings. Across spatial omics datasets from multiple platforms (>10 million cells in total), scaling experiments show improved representations with more training data and competitive clustering and embedding-quality performance with efficient computation. In a multi-sample human non-small-cell lung cancer (NSCLC) cohort, CellNiche identifies conserved and sample-specific tumor and immune microenvironments and captures localized spatial transitions. In four independent mouse brain atlases, CellNiche integrates 293 slices into a unified virtual brain map for cross-atlas annotation transfer and spatial refinement.