First Author | Jiang Y | Year | 2024 |
Journal | iScience | Volume | 27 |
Issue | 11 | Pages | 111173 |
PubMed ID | 39563897 | Mgi Jnum | J:358624 |
Mgi Id | MGI:7783223 | Doi | 10.1016/j.isci.2024.111173 |
Citation | Jiang Y, et al. (2024) Mapping and tracing Grem1(+) stromal cells in an Apc (Min/+) mouse utilizing cryopreserved intestinal sections prepared via modified Swiss-roll technique. iScience 27(11):111173 |
abstractText | 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. |