Stem and niche cell dynamics in normal and pathological conditions
Coherent tissue growth and repair require an interplay between stem cells and their local and systemic environment. The dynamics of this process remains poorly defined particularly at the intersection with disease. Cellular quiesc...
Coherent tissue growth and repair require an interplay between stem cells and their local and systemic environment. The dynamics of this process remains poorly defined particularly at the intersection with disease. Cellular quiescence is adopted by many adult stem cells, conferring them several features including a smaller cell volume and reduced metabolic demand, suggesting that quiescence preserves stem cell properties making them less responsive to external cues. We examined the status of skeletal muscle stem (MuSC) and niche cells during an influenza virus infection (lung) and cancer cachexia (tumour) in mice. Unexpectedly, quiescent MuSCs remodelled their cellular, metabolic, and transcriptome properties extensively, and tissue regeneration was impaired, prompting us to define a novel cell state, GPath. Whether GPath represents a coordinated response of stem cells to pathology, or uncontrolled deregulation, is unclear.
MuSCs exhibit remarkable diversity in gene regulation and function in distinct anatomical locations (head/limb). We discovered that cranial MuSCs display higher resistance to the pathologies compared to those in limb. These observations have led us into a novel area of research, to the best of my knowledge largely unexplored in model organisms and humans: how stem and niche cells in one organ respond to pathologies present at a distal site. We will examine the response of muscle and blood stem and niche cells to distal pathologies by defining their cellular, metabolic, molecular, epigenetic, and functional properties, and their modes of cell division. We will employ diverse multiomics approaches and novel medium/high-throughput intravital and ex vivo imaging pipelines. This work should provide new knowledge and tools to address an important, but under-investigated area of research where stem cell biology and pathologies converge. The knowledge gained will be widely applicable to other stem cell systems and inform on human pathologies.ver más
Seleccionando "Aceptar todas las cookies" acepta el uso de cookies para ayudarnos a brindarle una mejor experiencia de usuario y para analizar el uso del sitio web. Al hacer clic en "Ajustar tus preferencias" puede elegir qué cookies permitir. Solo las cookies esenciales son necesarias para el correcto funcionamiento de nuestro sitio web y no se pueden rechazar.
Cookie settings
Nuestro sitio web almacena cuatro tipos de cookies. En cualquier momento puede elegir qué cookies acepta y cuáles rechaza. Puede obtener más información sobre qué son las cookies y qué tipos de cookies almacenamos en nuestra Política de cookies.
Son necesarias por razones técnicas. Sin ellas, este sitio web podría no funcionar correctamente.
Son necesarias para una funcionalidad específica en el sitio web. Sin ellos, algunas características pueden estar deshabilitadas.
Nos permite analizar el uso del sitio web y mejorar la experiencia del visitante.
Nos permite personalizar su experiencia y enviarle contenido y ofertas relevantes, en este sitio web y en otros sitios web.