This research provides a comprehensive spatiotemporal transcriptomic atlas detailing the development of the human blood-brain barrier (BBB) from gestational weeks 6 to 21. By employing single-cell RNA sequencing and spatial transcriptomics, the authors identified that the human BBB begins to acquire its functional molecular signature at gestational week 8. The study highlights that neural progenitor cells and neurons trigger the expression of critical transporters in endothelial cells through CADHERIN-2 (CDH2) signaling. Furthermore, the researchers discovered that neural progenitor cells secrete PDGFD to drive the growth of mural cells, which are essential for structural integrity. Cross-species comparisons revealed that these developmental pathways are largely conserved between humans and mice. Finally, the protein H2A.Z.1 was identified as a vital regulator of both angiogenesis and the successful establishment of the barrier.

References:

• Li Z, Li Y, He Z, et al. Decoding the spatiotemporal development of the blood-brain barrier in human cortex[J]. Cell Stem Cell, 2026.