INSTINCT: Multi-sample integration of spatial chromatin accessibility sequencing data via stochastic domain translation

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 1, 2025

Recent advances in spatial epigenomic techniques have given rise to assay for transposase-accessible chromatin using sequencing (spATAC-seq) data, enabling the characterization of heterogeneity and information simultaneously. Integrative analysis multiple spATAC-seq samples, which no method has been developed, allows effective identification elimination unwanted non-biological factors within comprehensive exploration tissue structures providing a holistic landscape, thereby facilitating discovery biological implications study regulatory processes. In this article, we present INSTINCT, multi-sample INtegration Spatial chromaTIN accessibility data via stochastiC domain Translation. INSTINCT can efficiently handle high dimensionality eliminate complex noise batch effects samples through stochastic translation procedure. We demonstrate superiority robustness integrating across simulated scenarios real datasets. Additionally, highlight advantages identification, visualization, spot-type annotation, various downstream analyses, including motif enrichment analysis, expression partitioned heritability analysis. Complex between hinder their joint Here, authors integration. They show that effectively remove while preserving sufficient variations tasks.

Язык: Английский

A dorsal hippocampus-prodynorphinergic dorsolateral septum-to-lateral hypothalamus circuit mediates contextual gating of feeding

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 6, 2024

SUMMARY Adaptive regulation of feeding depends on linkage internal states and food outcomes with contextual cues. Human brain imaging has identified dysregulation a hippocampal-lateral hypothalamic area (LHA) network in binge eating, but mechanistic instantiation underlying cell-types circuitry is lacking. Here, we identify an evolutionary conserved discrete Prodynorphin ( Pdyn )-expressing subpopulation Somatostatin Sst inhibitory neurons the dorsolateral septum (DLS) that receives primarily dorsal, not ventral, hippocampal inputs. DLS( ) inhibit LHA GABAergic confer context- state-dependent calibration feeding. Viral deletion DLS mimicked effects seen optogenetic silencing INs, suggesting potential role for DYNORPHIN-KAPPA OPIOID RECEPTOR signaling food-seeking. Together, our findings illustrate how dorsal hippocampus evolved to recruit ancient circuit module through link information consumption. HIGHLIGHTS receive dense input from ventral Silencing hippocampus-DLS( )-LHA nodes abolishes context-conditioned necessary

Язык: Английский