Abstract
Prenatal nutrition can profoundly influence the brain development of offspring through mechanisms including epigenetic reprogramming. However, the complex interplay of maternal nutrition, neural development, and behaviors at the cellular level remains to be explored. Here, we report that gestational choline supplementation (GCS) in mice attenuates anxiety- and depression-like behaviors in male offspring (F1GCS). Multi-omics analysis reveals the comprehensive roles of GCS in diverse aspects of neuronal functions in F1GCS. Notably, the transcriptome, intercellular communication, and chromatin accessibility of immature granule neurons were altered in the hippocampus of F1GCS. This was accompanied by enhanced transcription and increased chromatin accessibility in glutamate signaling and suppressed transcription and reduced chromatin accessibility in MIF pathways in these neurons. Correlation analysis of cell populations with neuropsychiatric disorders showed a strong association between immature granule neurons and emotional disorders. Together, these findings provide molecular and cellular evidence supporting the effects of a widely used nutritional supplement in nutritional interventions.
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Data availability
All raw data have been deposited in the Genome Sequence Archive (GSA; accession number PRJCA043148) at the BIG Data Center, Beijing Institute of Genomics, Chinese Academy of Sciences. The processed snRNA-seq data are accessible via OMIX at the China National Center for Bioinformation/Beijing Institute of Genomics, Chinese Academy of Sciences (accession no. OMIX011041). Numerical source data for all graphs and charts are provided in the supplementary information and have been deposited at figshare (https://doi.org/10.6084/m9.figshare.31441492).
Code availability
All custom code used for the analyses presented in this paper is included in the Figshare dataset deposited alongside the source data. It is freely available under the https://doi.org/10.6084/m9.figshare.31441492.
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Acknowledgements
This work was supported by the National Key R&D Program of China (No. 2025YFA1309200), National Natural Science Foundation of China (Nos. 32270657, 32470630, and 32570726), the Natural Science Foundation of Beijing Municipality (No. 5242018), and State Key Laboratory of Animal Biodiversity Conservation and Integrated Pest Management (No. SKLA2508). The authors have no relevant financial or non-financial interests to disclose.
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Conceptualization: Y.W. and Z.S., Methodology: X.S., Y.L., M.W., X.Z., M.L., Q.L., W.X., Z.S., Y.W., Investigation: X.S., Y. L., M.W., X. Z., Q.L., W.X., Z.S., Y.W., Visualization: X.S. and Y.W., Supervision: Y.W. and Z.S. Writing original draft: X.S. and Y.W., Writing editing and review: X.S., Y.L., M.W., X.Z., M.L., Q.L., W.X., Z.S., Y.W.
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Shi, X., Li, Y., Wang, M. et al. Gestational choline supplementation regulates hippocampal granule neuron development and emotion-like behavior. Commun Biol (2026). https://doi.org/10.1038/s42003-026-09955-7
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DOI: https://doi.org/10.1038/s42003-026-09955-7
