Fig. 1: Cross-species evolutionary comparison of single-cell multiomics analysis of the M1.
From: Conserved and divergent gene regulatory programs of the mammalian neocortex
a, Illustration of the human M1 (left), created using BioRender. Dendrogram representing the evolutionary distance of each species in our study (right) from TimeTree69. b, Uniform manifold approximation and projection (UMAP)70 embeddings of 10x multiome RNA (top) and snm3C-seq DNA methylation (bottom) clustering, annotated by cell type (left) or species (right). The numbers in parentheses indicate the cell counts from each species. NP, near projecting neurons. ChC, Chandelier neurons. c, The fraction of each cell type from unbiased nucleus-sorted samples. Data are mean ± s.d. across donors (primates, n = 3) or pools (mouse, n = 8). d, The relative abundance between species for each cell type among its particular class (excitatory, inhibitory or non-neuron). Data are mean ± s.d. e, The WashU Comparative Epigenome Browser displaying an alignment between human (hg38; top, green) and macaque (rheMac10; bottom, blue) genomes with L2/3 IT excitatory data tracks for Hi-C, RNA, assay for transposase-accessible chromatin (ATAC) and mCG. f, The conservation index, showing GLS regression for NIPBL (GLS T statistic = 15.460) and GAREM1 (GLS T statistic = 3.673) between human and macaque coloured by cell type. The error bars indicate the 95% confidence interval calculated using GLS regression. g, The divergence index, showing differential expression between human and macaque in L5 IT neurons, PVALB neurons, ASCs and MGCs. NIPBL and GAREM1 are shown in red. FC, fold change. h, The relationship between the average conservation index across species and the average divergence index across species. Mammal-conserved genes are highlighted. i, The relationship between the average conservation index across species and the average divergence index across species. Human-biased genes are highlighted. j. Top significant GO analysis terms for non-ubiquitous mammal-conserved genes. Padj, adjusted P. k, Top significant GO analysis terms for non-ubiquitous human-biased genes in any cell type.
