Stretching the Limits: From Homeostasis to Stem Cell Plasticity in Wound Healing and Cancer

The document from February 26, 2018, reviews stem cell (SC) plasticity, emphasizing its role in wound healing and cancer. It explains that while adult SCs typically maintain homeostasis within their tissue lineage, they can become highly regenerative in response to injury. This plasticity is essential for wound repair but can be exploited by cancer cells to promote malignancy. The review covers molecular determinants of SC plasticity in the haematopoietic system, skin epithelium, and intestinal epithelium, and the influence of the SC niche. It discusses the regulation of hair follicle SCs (HFSCs) and intestinal SCs (ISCs) by various signaling pathways, including WNTs and BMPs, and the importance of the basement membrane and niche signals in SC behavior. The document also explores how chromatin dynamics and super-enhancers affect SC lineage choices, and how SC plasticity is context-dependent, influenced by the microenvironment, and can be altered in conditions like transplantation. It highlights that SCs can exhibit remarkable plasticity in response to stress, ensuring survival, but this plasticity can lead to malignancy in cancer, where SCs perceive continuous damage. Understanding SC plasticity and lineage infidelity could provide insights into targeted cancer therapies by exploiting the differences between normal SCs and cancer stem cells (CSCs). The document underscores the need for further research on SC niche dynamics, tissue damage impact on SC behavior, and the transition to sustained plasticity in cancer.