Microglia-neuron communication in health and disease
Microglia are the resident immune cells of the brain, display extensive heterogeneity, and contribute to a wide range of cellular processes in both homeostasis and disease. They play a major role in the pathogenesis of Alzheimer’s...
Microglia are the resident immune cells of the brain, display extensive heterogeneity, and contribute to a wide range of cellular processes in both homeostasis and disease. They play a major role in the pathogenesis of Alzheimer’s disease (AD), the leading cause of dementia and a major cause of mortality worldwide. Microglia closely interact with neurons and modulate their function with high regional specificity, making them potential culprits behind the neuronal damage in AD. However, exactly how microglia and neurons interact and communicate, and how these interactions change in disease is not known. I hypothesize that an early hallmark of AD is the changing interactions between microglia and neighboring cells such as neurons, which contributes to progress of the disease and ultimately results in synaptic and neuronal loss. I will test this in human microglia by using a unique human xenotransplantation model, whereby I transplant human pluripotent stem cell-derived microglial progenitors into the cortex of healthy and AD mice. Using RABID-seq combined with 10X Genomics to barcode microglia and subsequently trace their interactions with single-cell resolution, I will precisely map the interactions of distinct subsets of microglia and neurons, to determine homeostatic molecular networks and how cell-to-cell communication is altered in the early stages of AD. Ultimately, this will allow me to identify specific molecules and molecular pathways which can be manipulated to support a beneficial function in microglia, while blocking detrimental effects, to protect neurons and prevent, slow, or ameliorate the disease. Given that microglia are involved in normal brain development and multiple neurodegenerative diseases, finally dissecting how they interact with other cells of the CNS will be a valuable resource to the greater neuroscience community with implications for development, ageing, and disease.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.