Multiome Profiling Reveals Astrocyte and Neuroendocrine Targets of Prenatal Acoustic Programming in Zebra Finch Embryos

ABSTRACT: Prenatal sensory experience can program offspring phenotypes, yet the cell-type-specific regulatory mechanisms remain poorly understood. In zebra finches (Taeniopygia guttata), parental heat call vocalizations program offspring for thermal environments. To identify the cellular and epigenetic targets of this acoustic programming, we performed single-nucleus multiome sequencing (joint snRNA-seq and snATAC-seq) on medial hypothalamic punches from embryonic day 13 (E13) zebra finch embryos exposed to heat call or control call playback from E9–E13. We profiled 55,950 nuclei across 49 cell clusters representing 13 cell types. Differential chromatin accessibility analysis revealed a striking enrichment of chromatin remodeling in astrocytes (204 of 236 differentially accessible peaks), with Heat Call exposure predominantly increasing chromatin accessibility. chromVAR motif enrichment identified NFIC and AP-1 family transcription factors as top differentially active motifs in heat call embryos. Weighted gene co-expression network analysis identified an astrocyte module (Astro-M7) positively associated with heat call exposure, enriched for Notch signaling components. Cicero co-accessibility analysis revealed 9,502 heat call-specific chromatin loops involving 3,891 unique regulatory elements, concentrated at gliogenic regulators including NFIA, HES-5-like, and DLL1. Pseudotemporal trajectory analysis showed accelerated astrocyte developmental progression in heat call embryos. Additionally, transthyretin (TTR) showed sexually dimorphic, playback-associated expression in paraventricular nucleus glutamatergic neurons. Together, these findings reveal an epigenetic priming mechanism by which prenatal acoustic cues accelerate astrocyte maturation and reshape neuroendocrine programs in the developing hypothalamus.

ORGANISM(S): Taeniopygia guttata

PROVIDER: GSE322480 | GEO | 2026/03/06

REPOSITORIES: GEO