Cellular micro-environments, often referred to as "niches," play a pivotal role in orchestrating the destiny of individual cells. During normal cell turnover in organs, these specialized niches steer cells towards distinct paths of specialization. This intricate guidance ensures the functional diversity within the organ's cellular composition. Other niches, particularly those surrounding adult tissue stem cells are indispensable for maintaining stemness and thus the regenerative capabilities of organs. Even after catastrophic stem cell loss, specialized micro-environments (e.g. in the intestine) possess the remarkable capacity to reprogram differentiated cells, reverting them to an adult stem cell state. Consequently, cellular identity within epithelial organs is intrinsically interwoven with its spatial context. This spatial context emerges as a critical determinant in upholding organ functionality and facilitating regenerative processes, yet it holds equal relevance for disease.
Notably, similar to adult tissue stem cells, cancer cells also rely on specific micro-environments for their survival and expansion. This dependence is particularly pronounced during the initial stages of metastasis, when cancer cells find themselves without an established supportive tumor microenvironment at the distant site. The nature and suitability of this niche determine the fate of these cancer cells: death, dormancy, or aggressive proliferation. Even if cancer cells do find a suitable microenvironment for initial survival, the tumor cells need to remodel the cellular composition around them to ensure sufficient supply of nutrients, escape from immune detection and stimulation of growth promoting signaling pathways. At the same time, the changing niche conditions change cancer cell behavior. Success or failure of this co-evolution of metastatic cells and niche cells ultimately determines disease outcome and thus ultimately affects patient survival.
Despite the pivotal role of these cellular niches in normal physiology and disease, our understanding of their composition and the dynamic alterations they undergo during tissue regeneration or metastatic expansion is still very limited. One of the main reasons for this lack of knowledge is that few suitable tools exist to study these local cell communities with single-cell resolution. The EnviroTag project aims to close this knowledge gap and establish a novel reporter system, capable of selectively studying small and rare microenvironments such as those of adult tissue stem cells and early metastatic cancer cells. Our research objectives, which focus primarily on the gastrointestinal system, encompass not only the generation of a deeper understanding of microenvironmental dynamics but also the identification of novel regulatory mechanisms, signaling pathways, and specific cell types that may serve as potential targets for enhancing tissue regeneration or impeding the spread of metastatic disease.
