Transcriptome-scale spatial gene expression in the human dorsolateral prefrontal cortex

Maynard, K. E.; Collado-Torres, L.; Weber, L. M.; Uytingco, C.; Barry, B. K.; Williams, S. R.; Catallini, J. L.; Tran, M. N.; Besich, Z.; Tippani, M.; Chew, J.; Yin, Y.; Kleinman, J. E.; Hyde, T. M.; Rao, N.; Hicks, S. C.; Martinowich, K.; Jaffe, A. E.

doi:10.1101/2020.02.28.969931

bioRxiv · 10.1101/2020.02.28.969931

Transcriptome-scale spatial gene expression in the human dorsolateral prefrontal cortex

Maynard, K. E.·Collado-Torres, L.·Weber, L. M.·Uytingco, C.·Barry, B. K.·Williams, S. R.·Catallini, J. L.·Tran, M. N.·Besich, Z.·Tippani, M.·Chew, J.·Yin, Y.·Kleinman, J. E.·Hyde, T. M.·Rao, N.·Hicks, S. C.·Martinowich, K.·Jaffe, A. E.

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Abstract

We used the 10x Genomics Visium platform to define the spatial topography of gene expression in the six-layered human dorsolateral prefrontal cortex (DLPFC). We identified extensive layer-enriched expression signatures, and refined associations to previous laminar markers. We overlaid our laminar expression signatures onto large-scale single nuclei RNA sequencing data, enhancing spatial annotation of expression-driven clusters. By integrating neuropsychiatric disorder gene sets, we showed differential layer-enriched expression of genes associated with schizophrenia and autism spectrum disorder, highlighting the clinical relevance of spatially-defined expression. We then developed a data-driven framework to define unsupervised clusters in spatial transcriptomics data, which can be applied to other tissues or brain regions where morphological architecture is not as well-defined as cortical laminae. We lastly created a web application for the scientific community to explore these raw and summarized data to augment ongoing neuroscience and spatial transcriptomics research (http://research.libd.org/spatialLIBD). O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=138 SRC="FIGDIR/small/969931v1_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@fcf6borg.highwire.dtl.DTLVardef@1fab44dorg.highwire.dtl.DTLVardef@53629dorg.highwire.dtl.DTLVardef@6f3de5_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Maynard, K. E., Collado-Torres, L., Weber, L. M., Uytingco, C., Barry, B. K., Williams, S. R., Catallini, J. L., Tran, M. N., Besich, Z., Tippani, M., Chew, J., Yin, Y., Kleinman, J. E., Hyde, T. M., Rao, N., Hicks, S. C., Martinowich, K., Jaffe, A. E.. 2020-02-28. Transcriptome-scale spatial gene expression in the human dorsolateral prefrontal cortex. https://doi.org/10.1101/2020.02.28.969931

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