This paper utilizes single-cell RNA-sequencing (scRNA-seq) and Xenium spatial transcriptomics to create a detailed cellular and positional atlas of the developing human intestine, specifically focusing on previously undefined fibroblast populations (mesenchyme/stroma). The authors identify and map four distinct fibroblast subtypes: subepithelial cells (SECs), lamina propria fibroblasts (LPFs), submucosal fibroblasts (SMFs), and rare CXCL13+ fibroblasts—across various developmental stages and into adulthood. Furthermore, this atlas is employed to benchmark human intestinal organoids (HIOs) derived from pluripotent stem cells, revealing that transplanted HIOs successfully mimic the spatial organization of most fetal fibroblast populations but exhibit signs of transcriptional immaturity. The study establishes a foundational resource for understanding intestinal development and improving organoid engineering and disease modeling by emphasizing the critical importance of both cell type composition and spatial arrangement.

References:

• Johnson K F, Dong X, Tsai Y H, et al. Mapping mesenchymal diversity in the developing human intestine and organoids[J]. bioRxiv, 2025: 2025.07. 22.665939.