Interactive MERFISH data browser

“Seeing is Believing”

The Qian Lab uses spatial transcriptomics, a technique that maps gene activity while preserving a cell’s location, to create a high-resolution atlas of the developing human cerebral cortex. We found that its layered structure emerges much earlier than previously thought and that different brain areas form through distinct patterns—some gradually, others with sharper boundaries. These findings reshape our understanding of how the cortex is built and provide a foundation for studying neurodevelopmental disorders linked to disrupted brain organization.

A spatially resolved single-cell atlas of human cerebral cortex development

A spatial atlas of human fetal cerebral cortex development, encompassing 18 million single cells, spans eight cortical areas across four time points in the second and third trimesters. We utilized multiplexed error-robust fluorescence in situ hybridization (MERFISH), augmented with deep-learning-based cell segmentation, to examine the molecular, cellular, and cytoarchitectural development of human fetal cortex with spatially resolved single-cell resolution. We analyzed fetal human tissues from six individuals across gestational weeks (GW) 15, 20, 22, and 34, covering eight major cortical areas along the anterior-posterior (A-P) axis. We curated a panel of 300 genes for MERFISH analysis. This panel included canonical marker genes for major cell types, alongside genes selected for their cluster-specific enrichment in a published single-cell RNA sequencing (scRNAseq) dataset of the mid-gestation human fetal cortex. In total, we analyzed approximately 18 million single cells that met quality control criteria, and we integrated all experiments to cluster the cells based on their gene expression. Following a hierarchical strategy, we identified 8 cell classes, 33 cell types and 114 subtypes.

Refer to our recent publication for more detail.

Experiments included in the initial integrated analysis

Sample GW Region #Genes
UMB1117-F1b 15 PFC 300
UMB1117-F2a 15 PMC/M1 300
UMB1117-F2b 15 PMC/M1 300
UMB1117-P1 15 Par 300
UMB1117-T1 15 Temp 300
UMB1117-O1 15 Occi 300
FB080-F1 20 PFC 300
FB080-F2a 20 PFC 300
FB080-F2b 20 PFC 300
FB080-P1b 20 Par 300
FB080-P1a 20 Par 300
FB080-P2 20 Par 300
FB080-T1 20 Temp 300
FB080-O1a 20 Occi 300
FB080-O1b 20 Occi 300
FB080-O1c 20 Occi 300
FB080-O1d 20 Occi 300
FB121-F1 20 PFC 300
FB121-F2 20 PMC/M1 300
FB121-P1 20 Par 300
FB121-T1 20 Temp 300
FB121-P2 20 Par 300
FB121-O1 20 Occi 300
FB123-F1 22 PFC 300
FB123-F2 22 PFC 300
FB123-F3 22 PMC/M1 300
FB123-P1 22 Par 300
FB123-O1 22 Occi 300
FB123-O2 22 Occi 300
UMB5900-BA9 34 PFC 300
UMB5900-BA4 34 PMC/M1 300
UMB5900-BA123 34 Par 300
UMB5900-BA40a 34 Par 300
UMB5900-BA40b 34 Par 300
UMB5900-BA22 34 Temp 300
UMB5900-BA18 34 Occi 300
UMB5900-BA17 34 Occi 300

Additional experiments added subsequently (clustered separately)

Sample GW Region #Genes
UMB1367-P1 15 Par 300
UMB1367-O1 15 Occi 300
UMB1759-O1 18 Occi 960
UMB1031-O1 20 Occi 960
UMB1932-O1 21 Occi 960
UMB5958-BA17 adult, 22 years old Occi 300