Single-Cell Profiling Reveals the Impact of Genetic Alterations on the Differentiation of Inflammation-Induced Murine Colon Tumors
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Animal Model
2.2. Tumor Digestion and Single-Cell RNA Sequencing
2.3. Cells and Organoids
2.4. Generation of Stable Knockdown Organoids
2.5. RNA Isolation and Gene Expression
2.6. Immunohistochemistry (IHC)
2.7. Immunofluorescence and Imaging
2.8. Statistical Analysis
2.9. Computational Analysis
2.9.1. Single-Cell Data Pre-Processing and QC
2.9.2. Data Integration with Batch Correction
2.9.3. Subsetting and Visualizing Epithelial Data
2.9.4. Gene Ontology Enrichment Analysis
2.9.5. RNA Velocity
2.9.6. Simulated Gene Perturbation
3. Results
3.1. Single-Cell Profiling Identifies Cell Populations in Colon Tumors
3.2. Single-Cell Survey of Colon Tumor Epithelial Cells
3.3. BRAFV600E Mutation and Msh2 Deletion Alter Colon Tumor Epithelial Cell Composition
3.4. BRAFV600E Colon Tumors Are More Differentiated Than Min and Msh2 Deleted Tumors
3.5. BLM and MSH2KO Tumors Have Different Tumor Stem Cell Characteristics
3.6. CDX2 Is Involved in BRAFV600E Colon Tumor epithelial Cell Differentiation
4. Discussion
5. Conclusions
6. Limitations of the Study
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Ghobashi, A.H.; Lanzloth, R.; Ladaika, C.A.; Masood, A.; O’Hagan, H.M. Single-Cell Profiling Reveals the Impact of Genetic Alterations on the Differentiation of Inflammation-Induced Murine Colon Tumors. Cancers 2024, 16, 2040. https://doi.org/10.3390/cancers16112040
Ghobashi AH, Lanzloth R, Ladaika CA, Masood A, O’Hagan HM. Single-Cell Profiling Reveals the Impact of Genetic Alterations on the Differentiation of Inflammation-Induced Murine Colon Tumors. Cancers. 2024; 16(11):2040. https://doi.org/10.3390/cancers16112040
Chicago/Turabian StyleGhobashi, Ahmed H., Rosie Lanzloth, Christopher A. Ladaika, Ashiq Masood, and Heather M. O’Hagan. 2024. "Single-Cell Profiling Reveals the Impact of Genetic Alterations on the Differentiation of Inflammation-Induced Murine Colon Tumors" Cancers 16, no. 11: 2040. https://doi.org/10.3390/cancers16112040
APA StyleGhobashi, A. H., Lanzloth, R., Ladaika, C. A., Masood, A., & O’Hagan, H. M. (2024). Single-Cell Profiling Reveals the Impact of Genetic Alterations on the Differentiation of Inflammation-Induced Murine Colon Tumors. Cancers, 16(11), 2040. https://doi.org/10.3390/cancers16112040