Advances in 2D and 3D stem cell-derived models to study neurodegenerative diseases

TOPICAL COLLECTIONS

Guest Editors

Daniel Mordes

University of California, San Francisco, Institute for Neurodegenerative Diseases (IND), Dept. of Pathology

Daniel Mordes, MD, PhD, is an assistant professor in pathology at the University of California, San Francisco (UCSF) and an investigator at the Institute for Neurodegenerative Diseases. He completed clinical training in neuropathology and postdoctoral studies in Boston and was previously a junior faculty member at Harvard Medical School. His laboratory was recently established in the Weill Institute for Neurosciences building at UCSF. His team combines human stem cell models of disease and neuropathology to study the molecular mechanisms underlying amyotrophic lateral sclerosis and frontotemporal dementia and to pinpoint new therapeutic targets. Dr. Mordes also supports translational research on neurodegenerative diseases associated with alpha-synuclein pathology.

Angelique di Domenico

University of California, San Francisco, Institute for Neurodegenerative Diseases (IND), Dept. of Neurology

Angelique di Domenico, PhD, is an Assistant Adjunct Professor at the Institute for Neurodegenerative diseases of UCSF, working under the supervision of Nobel Laureate Dr. Stanley B. Prusiner. Dr. di Domenico received her Master’s in Neuroscience with a specialization in neurodegenerative diseases at King’s College London and continued her studies in the field of neurodegeneration, specializing in Parkinson’s disease, during her PhD years at the University of Barcelona and postdoc years at the New York Stem Cell Foundation (NYSCF). Her research has been focused primarily on glial cells and more specifically, on the roles that astrocytes play during the progression of neurodegeneration. In her paper titled “Patient-Specific iPSC-Derived Astrocytes Contribute to Non-Cell-Autonomous Neurodegeneration in Parkinson's Disease,” which was published in Stem Cell Reports (2019) and won the City of Barcelona Award in 2020 for its breakthroughs in the field, she demonstrated direct evidence for the first time that astrocytes have a neurotoxic role in LRRK2 Parkinson’s disease.

Collection Overview

Neurodegenerative disease prevalence is growing as the population ages, creating a great need to develop new therapeutic approaches, especially for Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS). Given the limitations of transgenic animal models and the restricted availability of human brain tissue samples, stem cell technology has transformed the field by providing a means to study these diseases in relevant human cell types, ultimately recapitulating human disease in a dish.

In this Methods Collection, we cover protocols for the directed differentiation of induced pluripotent stem cells into the highly specialized cells of the nervous system, neurons, and glia. This approach includes recent advances that generate multicellular, three-dimensional neural organoids aiming to recapitulate aspects of specific brain regions. These stem cell-based models are being utilized to understand neurodegenerative processes, including complex interactions between neurons and glial cells, and to support drug discovery efforts. Additionally, they are incorporated into strategies to elucidate the effects of genetic variants associated with neuropsychiatric diseases and neurodevelopmental disorders.