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

作者：Youheng Jiang, Fu Zhang, Yanfang Chen, Qunlong Jin, Yuan‐Han Yang, Zerong Lin, Changxue Li, Yunfei Gao, Zepeng Dong, He Yang, Yang He, Xinjun Mao, Yulong He, Yulong He, Qingyuan Zhang, Qi Zhang, Ningning Li · 发表于：iScience · 年份：2024 · DOI：10.1016/j.isci.2024.111173 · 被引用次数：4 · 研究领域：Cancer Cells and Metastasis、Chemokine receptors and signaling、3D Printing in Biomedical Research

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 Apc Min/+ mouse tumors at 12 weeks, compared to normal mucosa. Subsequent lineage tracing in Grem1-CreER T2 ; R26-LSL-tdTomato ; Apc Min/+ 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.