Tissue-resident stem cells are central to the homeostasis of many high-turnover tissues, including intestinal stem cells. The decline in their functionality is an established cause of tissue aging, whereas they are also susceptible to cancer transformation. In understanding the function and regulation of stem cells, the importance of supportive “niche” cells has become increasingly recognized. Yet, the role of niche cells in the context of health and disease remains poorly understood.
A central question that guides our research is:
How do niche cells contribute to gastrointestinal diseases?
To address this question, we have developed a suite of innovative tools:
- Organoid–niche cell co-culture systems to model stem cell-niche interactions in vitro.
- Novel reporter mouse models to visualize niche dynamics in vivo.
- An optimized platform for CRISPR/Cas9 genome editing of organoids and niche cells
- Orthotopic organoid transplantation to study disease processes in vivo
By integrating these tools, the Goto Lab is uncovering how niche cells drive gastrointestinal diseases, such as metastatic colorectal cancer and inflammatory bowel disease, as well as fundamental biological processes like stem cell aging. Our long-term goal is to leverage the dynamic interactions between niche cells and stem cells to develop novel treatments for colorectal cancer and other gastrointestinal diseases.