Using human stem cell–derived assembloids, Nguyen and her UCLA colleagues uncovered an early interaction that may help explain how the human cerebral cortex develops.
Research led by former International Foundation for Ethical Research (IFER) Graduate Fellow Claudia Nguyen has been published in Science, marking an important advance in the study of human brain development—and demonstrating the value of human-relevant research methods.
Nguyen, a postdoctoral fellow at the University of California, Los Angeles, served as first author of the study. Working in the laboratory of Dr. Aparna Bhaduri, she investigated how signals from the thalamus, a region deep within the brain, influence the development of the cerebral cortex—the part of the brain central to thought, memory and language.
The research focused on radial glia, neural stem cells that generate many of the neurons and support cells forming the cerebral cortex. These cells are especially important to understanding human brain development because certain radial glia are far more abundant in humans than in mice.
Recreating communication between developing brain regions
To study an early stage of brain development that is difficult to reproduce in animals, Nguyen and her colleagues grew separate human stem cell–derived organoids representing the thalamus and cortex. Organoids are three-dimensional clusters of cells that reproduce selected features of human tissues.
The researchers then fused the two organoids to create an “assembloid,” allowing the developing regions to interact in the laboratory.
Using this model, the team found that projections extending from the thalamus make direct physical contact with radial glia in the developing cortex. That contact influenced the stem cells to produce more excitatory neurons, particularly the upper-layer neurons that are greatly expanded in the human brain.
The researchers traced this interaction to NRXN1, a gene that helps nerve cells form connections. When they created assembloids using patient-derived cells carrying an NRXN1 mutation—mutations in this gene have been associated with autism spectrum disorder—the thalamic signals behaved differently and altered the balance between stem cells and the neurons they produced.
These findings provide a new way to investigate how disruptions during early development may affect formation of the cortex and contribute to neurodevelopmental conditions. The study is discussed in greater detail in the UCLA Newsroom.
Human-relevant science reveals human-specific biology
Mouse brains have far fewer outer radial glia than human brains, and thalamic projections reach the cortex on a different developmental timeline. By using human cells, the UCLA team could examine an interaction that may not exist in rodents in the same form.
“Claudia Nguyen’s research shows why replacing animal models with human-relevant approaches is essential to scientific progress,” said NAVS Director of Science and Research Programs Lauren Stein. “The developing mouse brain differs from the human brain in precisely the features her team needed to study, including the abundance of key neural stem cells and the timing of communication between brain regions. By connecting human thalamic and cortical organoids in an assembloid, the researchers uncovered an early developmental interaction that animal models may not capture. This is why NAVS supports IFER: our investment gives promising scientists the opportunity to develop innovative, human-cell-based models that can reveal more relevant biology while reducing reliance on animals.”
Nguyen received an IFER Graduate Fellowship for 2024–2025 to support her project, “The Role of Thalamic Afferents in Cortical Fate Specification in Fused Organoids.” The newly published findings reflect the very work the fellowship was created to advance: scientifically innovative research that improves our understanding of human biology while replacing or reducing the use of animals.
The International Foundation for Ethical Research supports early-career scientists developing, validating and implementing innovative alternatives to animal use in research, testing and education. Through its support of IFER, the National Anti-Vivisection Society invests in the next generation of researchers building a more humane—and more human-relevant—future for science.
