About the Qian Laboratory

The Qian Lab studies the development and disorders of the human cerebral cortex using two complementary approaches: direct analysis of human brain tissue through spatial transcriptomics, and modeling with human stem cell-derived brain organoids.

Why study the human cerebral cortex?

The cerebral cortex is what makes us human. It is the seat of higher cognition, language, and, most importantly, imagination. Compared to the more survival-focused regions like the brainstem or hypothalamus, the cortex is evolutionarily young and incredibly advanced in humans. But that same complexity makes it vulnerable. Disorders like autism and brain malformations often stem from disruptions in cortical development.

Our understanding of how the human cortex develops is still limited largely due to the field's focus on animal models, which often fall short at capturing human-specific features of brain development. That's why our work emphasizes human-based approaches and studies the human brain on its own terms.

How does the Qian Lab study the human cerebral cortex?

Brain organoids are tiny, self-organizing balls of cells, about 3-4 millimeters in diameter, each containing roughly 5 million cells. The organoids can be made from anyone's cells. Inside, they replicate many of the key features of the developing human cerebral cortex. Previous work by the Qian Lab team developed one of the first scalable and reproducible protocols to generate cerebral cortex–specific organoids, which led to one of the most highly cited papers in the field.

Nevertheless, like all models, organoids are approximations. The key is knowing how to benchmark them using reference maps based on human brain tissue.

Brain organoids provide a tractable experimental model to study human brain development.

Spatial Transcriptomics — techniques that preserve both gene expression and spatial context at single-cell resolution — are used to profile human tissue to create these reference maps. Using single-cell spatial transcriptomics (MERFISH), Dr. Qian and collaborators built an atlas of the developing human cortex from more than 18 million cells. The findings demonstrated boundaries between cortical layers and areas form much earlier than previously recognized, long before they are visible under a microscope, underscoring the unique power of spatial transcriptomics.

Spatial transcriptomics reveals the cell type and cytoarchitecture of the developing human cortex at single-cell resolution.

The Qian Lab will integrate these two approaches — modeling with organoids and direct analysis of human brain tissue — into a unified strategy. Postmortem brain tissue provides molecular and spatial ground truth, capturing what's really happening in human development and disease. But it's also static —depicting one snapshot in time that scientists can't manipulate.

Organoids, by contrast, are dynamic and experimentally tractable. They allow investigators to observe development as it unfolds, manipulate genetic or environmental factors, and test potential interventions. They are still imperfect models, but that's exactly why scientists need to benchmark them against real tissue.

Read more about the lab's projects to see what's next.