June Science on Tap with Ryan Hoffman: Brain Farming - Decoding How Our Brains Develop

Brain Farming - Using Stem Cells to Decode How Our Brains Develop - Ryan Hoffman, PhD Candidate, Haussler-Salama Lab, Molecular Biology, UCSC

The human body is made up of a community of close to 40 trillion cells. From a single zygote, over 200 diverse cell types are derived, each enacting a unique molecular program to spawn their specific function in your body. But how do these cells know which complicated series of genetic programs to enact, where, and when to enact them? My research is focused on how the human brain develops – specifically, how the most recently evolved region of the brain – the cerebral cortex – progresses through embryonic development and organizes. What is orchestrating neural stem cell differentiation, organization, and enacting their maturation programs to generate the fully functional, diverse landscape of the human cerebral cortex? I hypothesize that the innate interaction between the developing cerebral cortex and secreted signaling molecules in the underlying cerebrospinal fluid (CSF) plays a crucial role in the patterning and maturation of cerebral cell types. 

Using stem cell derived brain organoids, I generate and model the early developmental progression of the human cerebral cortex, as well as a lesser-known brain structure – the choroid plexus – which is responsible for the production and secretion of cerebrospinal fluid throughout life. I have established a protocol for the generation of human forebrain choroid plexus organoids (ChPOs), which will be used to construct a transcriptomic and secretion profile for the development of the choroid plexus and composition of embryonic CSF. The molecular patterning program implicated from the ChPO will be examined for its patterning potential on the cerebral cortex by exposing factors identified in the CSF to cerebral organoids from within an interior ventricular-like cavity. This will be done by using an aggregation technique that utilizes hydrogels and a biodegradable poly(lactic-co-glycolic acid) (PLGA) microsphere to engineer an interior cavity within a cerebral organoid, enabling the sustained release of various patterning factors to its interior. By directly evaluating the secreted factor program of ChPOs for inducing patterning effects on cerebral organoids, new insight on the complex molecular programs that gives rise to the human cerebral cortex and how those programs are being orchestrated may be revealed.