Fig. 4: Multimodal imaging reveals SE chromatin conformation in newly differentiated hippocampal neurons.
From: Temporally distinct 3D multi-omic dynamics in the developing human brain
a, Sequential imaging of 354 genomic regions on the median-sized chromosome 14 using 119 rounds of hybridization with three-colour imaging. b, 3D localization of each genomic region in a single nucleus. c, Reconstruction of single-molecule chromatin conformation for two chromosome 14 homologues in a single nucleus. d, Overview of the tissue section containing HPC and choroid plexus structures. FIM, fimbria; CP, choroid plexus. e, Example of multiplexed RNA imaging using MERFISH. f, UMAP dimensionality reduction of the RNA MERFISH profile and cell-type annotation. g, Spatial localization of annotated cell types. h, Spatial expression patterns of marker genes for cell types shown in g. i–n, Reconstruction of chromatin conformation for CA1 (i), dentate gyrus (j), excitatory neuron, choroid plexus cell types (k), ependymal cells (l), RG-1 (m) and RG-2 (n). o,p, Quantification of spatial distance in micrometres as a function of genomic distance in megabases for differentiated brain cell types (o) and RG progenitor cells (p). q, Imaging of nuclear architectural proteins and histone modifications. r, Correlation of active and repression protein markers across genomic loci on chromosome 14. s,t, Quantification of nuclear volume (s) and mean H3 K9 trimethylation intensity (t) on chromosome 14 in distinct cell types. n = 24,099 imaged cells. The centre of the box plot marks the median, with each box above or below the median representing 10 percentiles of the data distribution. u, Correlation of the spatial distance for loci with near-range and long-range genomic distance with nuclear volume or mean intensities for protein markers on chromosome 14. Abs., absolute. Scale bars, 5 μm (a,b,q), 250 μm (d,g), 20 μm (e).
