Matching Regional Diversity with Function: Unique Astrocyte Signals Mature Regionally Matched Neurons

Astrocytes are the most abundant cell type in the human brain, providing signals that are essential for all aspects of neuronal function and survival. But just as no two neurons are the same, astrocytes are incredibly diverse and specialized. Different types of astrocytes can provide different kinds of support and signals to the neurons they surround. In this proposal, Ullian and Rowitch will test whether the signals from different types of human astrocytes are necessary for the proper maturation and function of human iPSC-derived neurons. Their previous work in mouse models indicates that generating astrocytes that are matched to their partner neurons will be essential to studying and understanding human neuronal function in both health and disease.

Affiliated Investigators

David Rowitch, Ph.D.

University of California, San Francisco

Dr. Rowitch is Professor of Pediatrics and Neurosurgery and Chief of Neonatology at the University of California, San Francisco. His research focuses on overlapping mechanisms of glial development and human neurological disorders and brain cancer. Previously, Dr. Rowitch was a faculty member and investigator at Harvard Medical School and Dana-Farber Cancer Institute in Boston. Dr. has recently been given the title of Vice-chair in Pediatrics for Laboratory Research at UCSF.

Erik Ullian, Ph.D.

University of California, San Francisco

The Ullian lab has experience using a variety of tools to ask what effect astrocytes have on neuronal function. As a postdoctoral fellow in Ben Barres’ laboratory at Stanford University Dr. Ullian studied the role of astrocyte signals that regulate the formation, function, and stability of neuronal synapses. This work led the fundamental principal that astrocyte play important roles in synapse formation and function and further led to the identification of the first astrocyte secreted molecule that impacts synapse number. More recently, as PI on several NIH and private foundation sponsored research grants Dr. Ullian has continued to investigate mechanisms regulate synapse number and neuronal function, establishing techniques for the labeling of subsets of cells for in vivo and in vitro analysis. His lab has published electrophysiological and anatomical studies of neurons from many brain regions adapting physiology to study important questions about astrocyte or neuronal function. Additionally, he has utilized iPSCs to derive human neurons and astrocytes to study the functional consequences of human astrocyte signals on neuronal and circuit maturation and function. These combined studies have led to the Allen Family Foundation proposal to investigate human astrocyte heterogeneity as a key signal for the functional maturation of regionally matched human neurons.