SCENIC+: single-cell multiomic inference of enhancers and gene regulatory networks.

Joint profiling of chromatin accessibility and gene expression in individual cells provides an opportunity to decipher enhancer-driven gene regulatory networks (GRNs). Here we present a method for the inference of enhancer-driven GRNs, called SCENIC+. SCENIC+ predicts genomic enhancers along with candidate upstream transcription factors (TFs) and links these enhancers to candidate target genes. To improve both recall and precision of TF identification, we curated and clustered a motif collection with more than 30,000 motifs. We benchmarked SCENIC+ on diverse datasets from different species, including human peripheral blood mononuclear cells, ENCODE cell lines, melanoma cell states and Drosophila retinal development. Next, we exploit SCENIC+ predictions to study conserved TFs, enhancers and GRNs between human and mouse cell types in the cerebral cortex. Finally, we use SCENIC+ to study the dynamics of gene regulation along differentiation trajectories and the effect of TF perturbations on cell state. SCENIC+ is available at scenicplus.readthedocs.io .

Shared enhancer gene regulatory networks between wound and oncogenic programs.

Wound response programs are often activated during neoplastic growth in tumors. In both wound repair and tumor growth, cells respond to acute stress and balance the activation of multiple programs, including apoptosis, proliferation, and cell migration. Central to those responses are the activation of the JNK/MAPK and JAK/STAT signaling pathways. Yet, to what extent these signaling cascades interact at the cis-regulatory level and how they orchestrate different regulatory and phenotypic responses is still unclear. Here, we aim to characterize the regulatory states that emerge and cooperate in the wound response, using the Drosophila melanogaster wing disc as a model system, and compare these with cancer cell states induced by rasV12scrib-/- in the eye disc. We used single-cell multiome profiling to derive enhancer gene regulatory networks (eGRNs) by integrating chromatin accessibility and gene expression signals. We identify a 'proliferative' eGRN, active in the majority of wounded cells and controlled by AP-1 and STAT. In a smaller, but distinct population of wound cells, a 'senescent' eGRN is activated and driven by C/EBP-like transcription factors (Irbp18, Xrp1, Slow border, and Vrille) and Scalloped. These two eGRN signatures are found to be active in tumor cells at both gene expression and chromatin accessibility levels. Our single-cell multiome and eGRNs resource offers an in-depth characterization of the senescence markers, together with a new perspective on the shared gene regulatory programs acting during wound response and oncogenesis.

Cell type diversity in a developing octopus brain.

Octopuses are mollusks that have evolved intricate neural systems comparable with vertebrates in terms of cell number, complexity and size. The brain cell types that control their sophisticated behavioral repertoire are still unknown. Here, we profile the cell diversity of the paralarval Octopus vulgaris brain to build a cell type atlas that comprises mostly neural cells, but also multiple glial subtypes, endothelial cells and fibroblasts. We spatially map cell types to the vertical, subesophageal and optic lobes. Investigation of cell type conservation reveals a shared gene signature between glial cells of mouse, fly and octopus. Genes related to learning and memory are enriched in vertical lobe cells, which show molecular similarities with Kenyon cells in Drosophila. We construct a cell type taxonomy revealing transcriptionally related cell types, which tend to appear in the same brain region. Together, our data sheds light on cell type diversity and evolution in the octopus brain.