UCLA studies reveal how brain stem cells decide which neurons to build

Two studies from UCLA, published Thursday in the journals Cell and Science, have uncovered the metabolic and physical cues that guide radial glia — the stem cells responsible for building much of the human cerebral cortex — as they decide which types of brain cells to produce during prenatal development.newsroom.ucla+1

Metabolism as a Decision-Maker

The Cell study, led by co-first authors Jessenya Mil and Jose Soto and conducted in collaboration between the labs of Aparna Bhaduri and Heather Christofk, mapped the metabolism of the developing human cortex using donated tissue and stem cell-derived brain organoids. The researchers found that radial glia depend heavily on the pentose phosphate pathway, a process that converts glucose into materials for rapidly dividing cells.sciencedaily+1

When the team reduced glucose availability or disrupted that pathway, the stem cells shifted their output, generating more inhibitory neurons and cell types that normally appear later in development.newsroom.ucla+1

"What was surprising is that metabolism isn't just a passive thing that happens in the background," Bhaduri, an assistant professor of biological chemistry at the David Geffen School of Medicine at UCLA, said in a university news release. "It can really control how stem cells make decisions."newsroom.ucla

A Physical Signal from Deep in the Brain

The Science study, led by first author Claudia Nguyen, examined signals from the thalamus, a deep-brain structure that relays information throughout the nervous system. Using brain "assembloids" — fused thalamic and cortical organoids grown from human stem cells — the team found that projections from the thalamus make direct physical contact with radial glia far earlier than scientists had expected.scitechpulse+1

That contact prompted the stem cells to produce more excitatory neurons, particularly the upper-layer neurons most expanded in humans compared with other species. The researchers traced this interaction to NRXN1, a gene already linked to autism spectrum disorder. When assembloids were built from patient-derived cells carrying an NRXN1 mutation, the altered thalamic signals disrupted the balance between stem cells and the neurons they generated.newsroom.ucla+2

Implications for Disease and Development

Together, the studies suggest the developing brain is shaped by continuous communication between stem cells and their environment — both nutritional and structural. The metabolic findings could help scientists understand how maternal nutrition and metabolic disorders influence brain formation, while the thalamic contact work opens a potential avenue for investigating how early disruptions contribute to neurodevelopmental conditions.newsroom.ucla+1

"Radial glia are the coolest cells that have ever existed," Bhaduri said. "They're really key to making us human. But they're also at the center of many neurodevelopmental and neuropsychiatric disorders, as well as cancer."scitechpulse+1