In this stimulating episode, we welcome Dr. Klein, an esteemed cellular biologist, who delves into the intriguing world of mammalian intestinal stem cells (ISCs). The maintenance of tissue integrity largely depends on how stem cells react to changes in niche signals, and ISCs are no exception as they rely on Wnt ligands for self-renewal and proliferation. This delicate balancing act plays a crucial role in tissue regeneration after injury and in inflammatory bowel diseases, but if left unchecked, it could lead to colorectal cancer.

Dr. Klein discusses his intriguing findings about Discs large 1 (Dlg1), a protein previously thought to be integral to cell polarity but now found to be dispensable for that function and cellular turnover during intestinal homeostasis. However, Dlg1's role becomes critical when Wnt signaling intensifies. Employing RNA sequencing and genetic mouse models, Dr. Klein's research unveils the subtle workings of DLG1 in regulating the cellular response to increased canonical Wnt ligands via the transcriptional regulation of Arhgap31, which in turn deactivates CDC42, an effector of the non-canonical Wnt pathway.

In effect, this reveals a crucial DLG1-ARHGAP31-CDC42 axis that enables ISCs to respond to increased niche Wnt signaling, a discovery that can potentially enhance our understanding and treatment of gut-related ailments. Tune in for an intriguing conversation on the intricate cellular dynamics at play in our bodies.

Dr. Klein, Intestinal Stem Cells, Discs Large 1, Wnt Signaling, Tissue Integrity, RNA Sequencing, Genetic Mouse Models, Arhgap31, CDC42, Non-Canonical Wnt Pathway, Colorectal Cancer, Inflammatory Bowel Diseases.

A DLG1-ARHGAP31-CDC42 axis is essential for the intestinal stem cell response to fluctuating niche Wnt signaling https://doi.org/10.1016/j.stem.2022.12.008