Mapping and tracing Grem1 + stromal cells in an Apc Min/+ mouse utilizing cryopreserved intestinal sections prepared via modified Swiss-roll technique

• Published in: iScience 2024-11, Vol.27 (11), p.111173
• Main Authors: Jiang, Youheng, Fu, Zhang, Chen, Yanfang, Jin, Qunlong, Yang, Yanming, Lin, Zerong, Li, Changxue, Gao, Yunfei, Dong, Zepeng, He, Yang, Mao, Xinjun, He, Yulong, Zhang, Qingyuan, Zhang, Qi, Li, Ningning
• Format: Article
• Language: English
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2024.111173

Grem1 cancer-associated fibroblasts (CAFs) are crucial in colorectal cancer (CRC) development, yet technical challenges have limited understanding of their origins, spatiotemporal distribution, and potential roles. Here, we devised a custom mold, optimizing the gut Swiss-roll technique to create a single cryopreserved slide for comprehensive staining. Our integrated approach uncovered a marked increase in Grem1 CAFs within mouse tumors at 12 weeks, compared to normal mucosa. Subsequent lineage tracing in ; ; mice revealed that most Grem1 CAFs infiltrating the tumor core originated from Grem1 intestinal reticular stem cells (iRSCs). A minor subset of Grem1 CAFs, located in the submucosa, retained characteristics of Grem1 intestinal sub-epithelial myofibroblasts (ISEMFs). Altogether, CAFs derived from Grem1 iRSCs may serve as a principal stromal cell type driving early-stage CRC progression, while Grem1 ISEMFs contribute less from a more distant location. Hence, targeting Grem1 CAFs presents an early and promising therapeutic strategy in CRC.