UCLA: Thalamus Physically Touches Brain Stem Cells

Two separate studies by a team at the University of California, Los Angeles, published on September 4, 2026, in the journals Cell and Science, show how the stem cells that build the cerebral cortex decide what they will become. One study finds that glucose metabolism plays the decisive role. The other finds that a direct physical touch from extensions reaching in from the thalamus matters just as much, a contact the authors say most likely does not exist in rodents.

The cells at the center of both papers are radial glia, a type of stem cell that generates most of the neurons and support cells of the cerebral cortex during development, the part of the brain responsible for thought, memory and language. Radial glia mostly disappear before birth, but cells resembling them are known to reappear in brain tumors for reasons that are still not understood. “Radial glia are the coolest cells that have ever existed,” said Aparna Baduri, an assistant professor of biological chemistry at the David Geffen School of Medicine at UCLA and a co-author of both studies. “They’re really key to what makes us human. But they’re also at the center of a lot of neurodevelopmental and neuropsychiatric disorders, as well as cancer, so understanding how they make their decisions is one way to start understanding how those conditions arise.”

Glucose as a switch, not just fuel

The paper published in Cell, titled “Metabolic atlas of early human cortex reveals glycolytic remodeling and pentose phosphate pathway control of cell fate transitions” (DOI 10.1016/j.cell.2026.07.023), came out of a collaboration between the Baduri and Heather Christofk labs, with co-first authors Jessenya Mill and Jose Sota. The team built a metabolic atlas of the early human cortex, drawing on donated human tissue and on brain organoids grown from stem cells.

Unexpectedly, the researchers recorded a rise in glycolysis and pentose phosphate pathway activity right at the late stage of neurogenesis, the process that generates new neurons. When the team reduced glucose availability in the organoids or blocked that metabolic pathway, using drugs or genetic tools, the stem cells changed the mix of cells they produced: more outer radial glia and more inhibitory neurons appeared, cell types that normally show up later in development. “What was surprising was that metabolism isn’t just something passive happening in the background,” Baduri said. “It can actually control how stem cells make decisions.”

The thalamus arrives early, for a reason that was unclear until now

The second study, published in Science and led by first author Claudia Nguyen, looks at an entirely different source of information: signals from the thalamus, a structure deep in the brain that relays information through the nervous system. Earlier anatomical studies had shown that extensions from the thalamus reach the cortex long before final connections to target neurons are formed, which left open the question of what that early presence was for.

Using models called assembloids, fused structures built from stem cells, the team showed that thalamic extensions make direct physical contact with radial glia. That contact pushed the cells to produce more excitatory neurons, the cortex’s main signaling cells, particularly the ones in the upper layers that are most developed in humans specifically. “We already knew these projections affected how the cortex develops,” Baduri explained. “What we specifically found is that this influence comes through an actual physical connection between the projections and the radial glia, a point of contact that just hadn’t been identified before, and one that most likely doesn’t exist in rodents.”

The researchers linked that connection to the gene NRXN1, which helps neurons build connections with each other and whose mutations have been tied to autism spectrum disorders. When the team built assembloids from cells of patients carrying an NRXN1 mutation, the thalamic signals in those models did not behave as they did in unmutated cells, throwing off the balance between the stem cells and the neurons they generate.

Both studies were funded by the National Institutes of Health, the National Science Foundation and the Brain and Behavior Research Foundation, among other donors. “Ultimately, these studies give us a look under the hood at how these cells make decisions,” Baduri said.

Both studies were carried out on donated human tissue, organoids and assembloids, models grown in the lab rather than in a living, developing brain inside the womb. That means what has been shown is a link between metabolism, physical contact and cell fate within these models, not proof that the same mechanism works the same way throughout an entire human pregnancy. The claim that physical contact between the thalamus and radial glia “most likely does not exist” in rodents rests on earlier anatomical findings about the rodent brain, not on a direct comparison carried out within these two studies.