Transcriptomic cytoarchitecture reveals principles of human neocortex organization

• 成果类型: Article
• 署名作者: Jorstad, Nikolas L.; Close, Jennie; Johansen, Nelson; Yanny, Anna Marie; Barkan, Eliza R.; Travaglini, Kyle J.; Bertagnolli, Darren; Campos, Jazmin; Casper, Tamara; Crichton, Kirsten; Dee, Nick; Ding, Song-Lin; Gelfand, Emily; Goldy, Jeff; Hirschstein, Daniel; Kiick, Katelyn; Kroll, Matthew; Kunst, Michael; Lathia, Kanan; Long, Brian; Martin, Naomi; Mcmillen, Delissa; Pham, Trangthanh; Rimorin, Christine; Ruiz, Augustin; Shapovalova, Nadiya; Shehata, Soraya; Siletti, Kimberly; Somasundaram, Saroja; Sulc, Josef; Tieu, Michael; Torkelson, Amy; Tung, Herman; Callaway, Edward M.; Hof, Patrick R.; Keene, C. Dirk; Levi, Boaz P.; Linnarsson, Sten; Mitra, Partha P.; Smith, Kimberly; Hodge, Rebecca D.; Bakken, Trygve E.; Lein, Ed S.
• 署名单位: Allen Institute for Brain Science; Karolinska Institutet; Salk Institute; Icahn School of Medicine at Mount Sinai; University of Washington; University of Washington Seattle; Cold Spring Harbor Laboratory
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-13689
• DOI: 10.1126/science.adf6812
• 发表日期: 2023-10-13
• 页码: 176-+
• 关键词: meynert cells project; motor cortex; superior colliculus; human brain; neurons; atlas; monkey; areas; architecture; morphology

摘要

INTRODUCTION The human neocortex is generally organized into six layers of neurons but the size and cellular composition of these layers varies across the cortex, and this variation is thought to underlie differences in connectivity that impart specific functional specialization to distinct cortical areas. However, the degree to which cortical areas have a canonical versus noncanonical organization has proved difficult to reliably quantify. Single-nucleus and spatial transcriptomic methods enable high-resolution characterization of the cellular structure of the human neocortex providing a means to quantitatively compare the molecular and cellular structure and specialization of distinct cortical areas.RATIONALE Eight cortical areas that are representative of major variation in cellular architecture and include primary sensory and association cortices were sampled using single-nucleus transcriptomics to generate a dataset comprised of more than 1.1 million nuclei.RESULTS Nuclei were grouped based on gene expression similarity into one of 24 cellular subclasses, which were found in all cortical areas. Layer 4 intratelencephalic excitatory neurons were present even in agranular areas that lacked a histologically distinct layer 4, suggesting a common subclass-level cellular blueprint across the cortex. However, gene expression and subclass proportions varied substantially between cortical areas, with more differences in excitatory projection neurons than inhibitory neurons. All non-neuronal subclasses were shared across cortical areas but their laminar distributions varied between areas, and astrocytes also expressed regional marker genes. Variation as a function of rostrocaudal location in the cortex was a clear organizational feature where neighboring cortical areas were most similar, in line with previous observations of gene expression similarity by topographic proximity in the cortex. At a finer cell-type level of analysis, area-enriched and area-specific cell types were apparent in multiple cortical areas, but most notably in the primary visual cortex (V1) that had many distinct excitatory neuron types and several distinct inhibitory neuron types that reflect the specialized cellular architecture of this area in humans and other primates. V1 specialized inhibitory cell types were mostly Somatostatin-expressing neurons likely originating from the medial ganglionic eminence during development. Layer 4 in V1, which is visibly enlarged and has multiple sublayers, was notably different from other areas with discrete sublaminar distributions of specialized excitatory and inhibitory neurons revealed by spatial transcriptomics.CONCLUSION A common set of cell types are found across human cortical areas that have diverse functions. Excitatory projection neurons exhibit large spatial gradients and regional differences in proportions, laminar distributions, and gene expression that are less pronounced in inhibitory neurons or non-neuronal cells. V1 is molecularly distinct from other cortical areas and several excitatory and inhibitory neuronal types are found only in V1. The ratio of excitatory to inhibitory neurons in V1 is also more than double that of other cortical areas, reflecting specialization of the human cortex for processing visual information.