How the Human Brain’s Master Stem Cells Listen to Nutrients and Neighbors

When a human baby’s brain is still inside the womb, a handful of extraordinary stem cells called radial glia are busy laying down the groundwork for everything we later call thought, memory and language. These cells are like master architects: they decide which types of neurons and support cells to generate, when to produce them, and even how the cerebral cortex expands to become the convoluted organ unique to our species.

“Radial glia are the coolest cells that have ever existed,” says Aparna Bhaduri, an assistant professor of biological chemistry at UCLA’s David Geffen School of Medicine. She’s quick to add that the same cells sit at the heart of many neurodevelopmental disorders, psychiatric conditions and even certain brain cancers. Understanding what nudges them to make one decision over another could therefore help explain a lot of puzzling disease mechanisms.

Two fresh studies, published in Cell and Science, dive into exactly that question. The researchers used a blend of donated human fetal tissue, lab‑grown brain organoids, and so‑called “assembloids” (fused organoids that mimic interactions between different brain regions). Their findings point to two very different kinds of instructions that radial glia heed: the way they process nutrients, and the physical touch they receive from a neighboring brain structure called the thalamus.

Metabolism as a decision‑maker

In the Cell paper, Bhaduri’s lab teamed up with Heather Christofk’s group. Co‑first authors Jessenya Mil and Jose Soto mapped out a metabolic atlas of the developing human cortex, comparing actual fetal tissue with stem‑cell‑derived organoids. What they discovered was unexpected – radial glia lean heavily on the pentose‑phosphate pathway, a glucose‑driven process that supplies building blocks for rapidly dividing cells.

When the scientists cut back on glucose or interfered with that pathway, the stem cells didn’t just slow down; they actually changed their output. The radial glia started producing more inhibitory neurons and other cell types that normally appear later in development. As Bhaduri puts it, “metabolism isn’t just a passive background hum; it can actively steer stem‑cell fate.” This insight could help explain how maternal nutrition, diabetes or other metabolic conditions ripple out to affect a child’s brain formation.

Physical cues from the thalamus

The second study, appearing in Science, took a very different angle. First author Claudia Nguyen focused on the thalamus – the deep brain hub that relays sensory information across the nervous system. Long before thalamic fibers make their final synaptic connections in the cortex, they extend thin projections that actually touch radial glia.

Using assembloids that fuse thalamic and cortical organoids, the UCLA team saw that this direct contact nudges radial glia toward generating more excitatory neurons, especially the upper‑layer cells that are dramatically expanded in humans compared with rodents. The link hinges on the gene NRXN1, best known for building neuronal connections and previously associated with autism spectrum disorder. When NRXN1 was disrupted, the thalamic influence waned, and the cortical progenitors reverted to a more default pattern.

“We already knew thalamic projections shape cortex development,” Bhaduri says, “but now we see that the effect comes from an actual physical handshake with radial glia—a handshake that likely doesn’t happen in mice.”

Together, these studies reframe radial glia’s environment not as a passive backdrop but as an active driver of brain development. Metabolic signals and tactile cues from neighboring regions both feed into the decision‑making circuitry that builds the human cortex.

Beyond basic science, the work offers new angles for tackling disorders where this choreography goes awry – from autism and schizophrenia to brain tumors that appear to hijack radial‑glia‑like cells. By mapping the metabolic landscape and pinpointing the thalamic‑glial handshake, researchers now have clearer targets for future therapies.