Mapping and tracing Grem1+ stromal cells in an ApcMin/+ mouse utilizing cryopreserved intestinal sections prepared via modified Swiss-roll technique
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
Affiliations
Youheng Jiang
Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, China; Digestive Diseases Center, Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, China
Zhang Fu
Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, China; Department of Geriatrics, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen 518107, China
Yanfang Chen
Digestive Diseases Center, Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, China
Qunlong Jin
Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, China; Digestive Diseases Center, Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, China
Yanming Yang
Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, China
Zerong Lin
Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, China
Changxue Li
Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, China; Digestive Diseases Center, Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, China
Yunfei Gao
Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, China; Department of Otolaryngology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, China
Zepeng Dong
Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, China
Yang He
School of Mechanical Engineering and Automation, Harbin Institute of Technology, Shenzhen 518107, China
Xinjun Mao
Department of Anesthesiology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, China
Yulong He
Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, China; Digestive Diseases Center, Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, China; Corresponding author
Qingyuan Zhang
Digestive Diseases Center, Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, China; Corresponding author
Qi Zhang
Department of Anesthesiology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, China; Corresponding author
Ningning Li
Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, China; China-UK Institute for Frontier Science, Shenzhen 518107, China; Corresponding author
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.
