106 / 2024-10-28 10:16:42

Single-cell spatial chromatin architecture profiling in mammalian brains

single cell 3D genome,brain

The 3D chromatin architecture is crucial for understanding gene regulatory programs in the development and disease. However, the direct mapping genome-wide 3D chromatin structures while retaining spatial information in tissues is still lacking. Here, we develop a spatial Hi-C method to resolve chromatin architecture profiling in situ tissue at single-cell resolution. The spatial Hi-C alone can obviously distinguish different cell niches in mammalian brains. Furthermore, according to single-cell spatial Hi-C profiles during the mouse brain development, we observe a decreased trend of the long-range interactions along the inside-to-outside radial direction on coronal brain sections, which is associated with neuronal differentiation states. Additionally, there exist five subtypes of cerebellar granular cells with distinguished 3D chromatin structure, presenting specific spatial locations in the adult mouse cerebellum lobule. In all, spatial Hi-C provides a valuable tool to study spatial 3D genome regulation in complex tissues.