Integrated single cell and unsupervised spatial transcriptomic analysis defines molecular anatomy of the human dorsolateral prefrontal cortex

Louise Huuki-Myers; Abby Spangler; Nick Eagles; Kelsey D Montgomery; Sang Ho Kwon; Boyi Guo; Melissa Grant-Peters; Heena R Divecha; Madhavi Tippani; Chaichontat Sriworarat; Annie B Nguyen; Prashanthi Ravichandran; Matthew N Tran; Arta Seyedian; PsychENCODE consortium; Thomas M Hyde; Joel E Kleinman; Alexis Battle; Stephanie C Page; Mina Ryten; Stephanie C Hicks; Keri Martinowich; Leonardo Collado-Torres; Kristen R Maynard

doi:10.1101/2023.02.15.528722

Integrated single cell and unsupervised spatial transcriptomic analysis defines molecular anatomy of the human dorsolateral prefrontal cortex

bioRxiv [Preprint]. 2023 Feb 15:2023.02.15.528722. doi: 10.1101/2023.02.15.528722.

Authors

Louise Huuki-Myers¹, Abby Spangler¹, Nick Eagles¹, Kelsey D Montgomery¹, Sang Ho Kwon^{1

2}, Boyi Guo³, Melissa Grant-Peters^{4

5}, Heena R Divecha¹, Madhavi Tippani¹, Chaichontat Sriworarat^{1

2}, Annie B Nguyen¹, Prashanthi Ravichandran⁶, Matthew N Tran¹, Arta Seyedian¹; PsychENCODE consortium; Thomas M Hyde^{1

7

8}, Joel E Kleinman^{1

7}, Alexis Battle^{6

9

10

11}, Stephanie C Page¹, Mina Ryten^{4

5

12}, Stephanie C Hicks^{3

11}, Keri Martinowich^{1

2

7}, Leonardo Collado-Torres¹, Kristen R Maynard^{1

2

7}

Affiliations

¹ Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.
² The Solomon H. Snyder Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, USA.
³ Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
⁴ Genetics and Genomic Medicine, Great Ormond Street Institute of Child Health, University College London, London, UK.
⁵ Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, USA.
⁶ Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA.
⁷ Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA.
⁸ Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
⁹ Department of Computer Science, Johns Hopkins University, Baltimore, MD, USA.
¹⁰ Department of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA.
¹¹ Malone Center for Engineering in Healthcare, Johns Hopkins University, Baltimore, MD, USA.
¹² NIHR Great Ormond Street Hospital Biomedical Research Centre, University College London, London, UK.

Abstract

Generation of a molecular neuroanatomical map of the human prefrontal cortex reveals novel spatial domains and cell-cell interactions relevant for psychiatric disease. The molecular organization of the human neocortex has been historically studied in the context of its histological layers. However, emerging spatial transcriptomic technologies have enabled unbiased identification of transcriptionally-defined spatial domains that move beyond classic cytoarchitecture. Here we used the Visium spatial gene expression platform to generate a data-driven molecular neuroanatomical atlas across the anterior-posterior axis of the human dorsolateral prefrontal cortex (DLPFC). Integration with paired single nucleus RNA-sequencing data revealed distinct cell type compositions and cell-cell interactions across spatial domains. Using PsychENCODE and publicly available data, we map the enrichment of cell types and genes associated with neuropsychiatric disorders to discrete spatial domains. Finally, we provide resources for the scientific community to explore these integrated spatial and single cell datasets at research.libd.org/spatialDLPFC/.

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Abstract

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