Wagstyl, Konrad;
Adler, Sophie;
Seidlitz, Jakob;
Vandekar, Simon;
Mallard, Travis T;
Dear, Richard;
DeCasien, Alex R;
... Raznahan, Armin; + view all
(2024)
Transcriptional cartography integrates multiscale biology of the human cortex.
eLife
, 12
, Article RP86933. 10.7554/elife.86933.3.
(In press).
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Abstract
The cerebral cortex underlies many of our unique strengths and vulnerabilities, but efforts to understand human cortical organization are challenged by reliance on incompatible measurement methods at different spatial scales. Macroscale features such as cortical folding and functional activation are accessed through spatially dense neuroimaging maps, whereas microscale cellular and molecular features are typically measured with sparse postmortem sampling. Here, we integrate these distinct windows on brain organization by building upon existing postmortem data to impute, validate, and analyze a library of spatially dense neuroimaging-like maps of human cortical gene expression. These maps allow spatially unbiased discovery of cortical zones with extreme transcriptional profiles or unusually rapid transcriptional change which index distinct microstructure and predict neuroimaging measures of cortical folding and functional activation. Modules of spatially coexpressed genes define a family of canonical expression maps that integrate diverse spatial scales and temporal epochs of human brain organization – ranging from protein–protein interactions to large-scale systems for cognitive processing. These module maps also parse neuropsychiatric risk genes into subsets which tag distinct cyto-laminar features and differentially predict the location of altered cortical anatomy and gene expression in patients. Taken together, the methods, resources, and findings described here advance our understanding of human cortical organization and offer flexible bridges to connect scientific fields operating at different spatial scales of human brain research.
| Type: | Article |
|---|---|
| Title: | Transcriptional cartography integrates multiscale biology of the human cortex |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.7554/elife.86933.3 |
| Publisher version: | https://doi.org/10.7554/eLife.86933.3.sa0 |
| Language: | English |
| Additional information: | © This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Imaging Neuroscience |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10187679 |
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