Human choroid plexus organoids to investigate unexplored mechanisms and secreted biomarkers in neurodevelopmental disease
Project Overview
Our brains are built by neural stem cells (NSCs), which produce all the neurons and other specialized cells that form the brain and execute its functions. We understand many of the internal processes NSCs use to control which cells they will produce and when. However, we also know the environment NSCs find themselves in can impact their decisions, but our understanding of this aspect is very limited. NSCs are found in a unique location in the brain, surrounding the ventricles. These are fluid-filled passages in which molecular factors circulate and can influence the properties of NSCs that they contact. This fluid, known as cerebrospinal fluid (CSF), is produced by a specialized tissue called the choroid plexus that resides deep within the brain. Abundant in metabolites, proteins and growth factors, the composition of CSF is thought to impact brain development by influencing NSCs and may therefore be an important aspect of brain diseases. Since NSCs and other neural cells can themselves communicate with CSF, it is also thought this fluid may be a source of disease-associated biomarkers.
My lab develops models of genetic brain diseases using human stem cells. Recently, it became possible to engineer choroid plexus tissue with stem cells. Incredibly, these tissues produce fluid that is very similar to human CSF. The choroid plexus and CSF are very difficult to access in humans, thus this technology offers us a way to finally study how this system impacts brain development and disease, and to determine if CSF fluid houses valuable biomarkers relevant to brain diseases. We will produce choroid plexus tissues from our stem cells with mutations that cause rare epilepsy and early-onset degenerative diseases and determine if the CSF-like fluid they secrete impacts brain development, and if this fluid contains molecular factors that reflect key aspects of these diseases.
Principal Investigator
Lisa Julian , Simon Fraser University