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

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.
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