The human brain's earliest stem cells are not just passive builders. They actively respond to two very different kinds of instructions: how they process glucose and physical contact with signals from another brain region. This discovery, made by researchers at the University of California, Los Angeles, reveals a hidden layer of decision-making that shapes the cerebral cortex before birth.
Stem Cells That Listen to Food and Touch
Radial glia are the stem cells responsible for producing much of the cerebral cortex, the brain area linked to thought, memory, and language. These cells are also thought to drive the unusually large expansion of the human cortex compared to other species. The UCLA team found that radial glia change their behavior based on how they metabolize nutrients and on direct physical signals arriving from the thalamus, a region deep in the brain that relays sensory information.
Two Studies, One Deeper Understanding
In one study, published in the journal Cell, researchers built a detailed map of metabolism in the developing human cortex. They analyzed donated human tissue and brain organoids grown from stem cells. The results showed that metabolism does not just support brain development in the background. It can actively influence which kinds of cells are produced. Radial glia depend heavily on the pentose phosphate pathway, a process that uses glucose to make materials for rapidly dividing cells. When the researchers lowered the available glucose, the cells' behavior changed.
In a second study, published in Science, the team focused on physical signals from the thalamus. They fused thalamic and cortical organoids to study how neurons from the thalamus influence immature cortical progenitor cells. These signals can alter which types of neurons are produced, including upper-layer neurons that are especially prominent in humans.
Why This Matters Locally
The research was led by Aparna Bhaduri, an assistant professor of biological chemistry at the David Geffen School of Medicine at UCLA. Her lab collaborated with Heather Christofk's lab, with co-first authors Jessenya Mil and Jose Soto. The team studied donated human tissue and lab-grown organoids to understand how radial glia make their decisions. Bhaduri noted that radial glia are key to making us human, but they are also at the center of many neurodevelopmental and neuropsychiatric disorders, as well as cancer. Understanding how these cells make choices could help explain how such conditions arise.
Most radial glia disappear before birth, but similar cells can later reappear in brain cancers for reasons that remain unclear. The new findings offer a closer look at the fundamental processes that build the human brain, potentially opening doors to understanding developmental disorders and cancers that involve these remarkable stem cells.
