| Autor: |
Youheng Jiang, Zhang Fu, Yanfang Chen, Qunlong Jin, Yanming Yang, Zerong Lin, Changxue Li, Yunfei Gao, Zepeng Dong, Yang He, Xinjun Mao, Yulong He, Qingyuan Zhang, Qi Zhang, Ningning Li |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
iScience, Vol 27, Iss 11, Pp 111173- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2589-0042 |
| DOI: |
10.1016/j.isci.2024.111173 |
| Popis: |
Summary: 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 ApcMin/+ mouse tumors at 12 weeks, compared to normal mucosa. Subsequent lineage tracing in Grem1-CreERT2; R26-LSL-tdTomato; ApcMin/+ 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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