Integrative single-nucleus multiomic, CUT&Tag, and bulk RNA-seq profiling of human and mouse prefrontal cortex reveals gene regulatory mechanisms of cortical development and Meis2 function

The development of the prefrontal cortex (PFC) is governed by coordinated transcriptional and epigenomic regulatory programs. To comprehensively characterize these processes, we generated an integrative multi-modal dataset combining single-nucleus multiomic (snRNA-seq and snATAC-seq), CUT&Tag, and bulk RNA-seq data from human and mouse PFC. Single-nucleus multiomic data from human mid-fetal dorsolateral prefrontal cortex (dlPFC) samples and mouse postnatal day 1 (P1) medial prefrontal cortex (mPFC) and motor cortex (MC) and provide matched gene expression and chromatin accessibility profiles across diverse cell types. Complementary CUT&Tag experiments profiling key transcription factors (RARA, RARB, RXRG, MEIS2) and histone modifications (H3K27ac, H3K4me3) further define regulatory elements and transcriptional control landscapes. To investigate the functional role of Meis2, bulk RNA-seq was performed on mouse P0 medial prefrontal cortex (mPFC) from control and Meis2 conditional knockout (cKO) samples. These data enable the identification of gene expression changes associated with Meis2 perturbation. Together, this integrated dataset provides a resource for studying gene regulatory networks underlying cortical development and for linking transcription factor activity to downstream gene expression programs across species.