Transcriptional regulatory programs underlying cellular and regional specialization in the late-gestation porcine brain

Late gestation is critical for foetal brain organization, yet the regional determinants driving brain specialization remain unclear. Here, we construct a transcriptomic atlas of the porcine brain at embryonic Day 110, integrating single-cell and single-nucleus RNA sequencing across 27 anatomical regions. Neuronal analysis uncovers neurogenesis signatures across multiple regions, including the corpus callosum, olfactory bulb, striatum, hippocampus, cerebellum, and frontal cortex, and implicates ELF2 as a regulator of hippocampal neurogenesis.

Astrocyte profiling reveals region-specific molecular programs governed by combinatorial transcription factors. Microglia exhibit bifurcating developmental fates, comprising a NEUROD1/PAX6-driven neuronal-enriched branch and a FOSB/ATF3-driven immune-related branch. Furthermore, oligodendrocyte lineage analysis identifies immune-associated subtypes, with FOS and ENO1 implicated as regulators of oligodendrocyte differentiation.

Finally, cross-species integration demonstrates conserved cellular identities among pigs, humans, and mice. Collectively, this high-resolution atlas elucidates the dynamic transcriptional programs underlying regional specialization in the mammalian brain during late-gestation development. We thank Lusheng Huang for conceptualizing, designing, and supervising the project and Ying Su for preparing the antibodies for sequential double immunofluorescence staining of paraffin sections.

This work was Supported by Key Project of Jiangxi Provincial Key Research and Development Program (Grant No. 20243BCC31002) and National Modern Agricultural Industry Technology System (CARS-35). These authors contributed equally: Jiacheng Wei, Ping Liu. National Key Laboratory for Swine Genetic Improvement and Germplasm Innovation, Ministry of Science and Technology of China, Jiangxi Agricultural University, Nanchang, China The authors declare no competing interests.

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