GeniOmics

Public knowledge document

Spatial transcriptomics reveals human cortical layer and area specification.

The human cerebral cortex is composed of six layers and dozens of areas that are molecularly and structurally distinct 1-4 . Although single-cell transcriptomic studies have advanced the molecular characterization of human cortical development, a substantial gap exists owing to the loss of spatial context during cell dissociation 5-8 . Here we used multiplexed error-robust fluorescence in situ hybridization (MERFISH) 9 , augmented with deep-learning-based nucleus segmentation, to examine the molecular, cellular and cytoarchitectural development of the human fetal cortex with spatially resolved single-cell resolution. Our extensive spatial atlas, encompassing more than 18 million single cells, spans eight cortical areas across seven developmental time points. We uncovered the early establishment of the six-layer structure, identifiable by the laminar distribution of excitatory neuron subtypes, 3 months before the emergence of cytoarchitectural layers. Notably, we discovered two distinct

Open platform knowledge

Spatial transcriptomics reveals human cortical layer and area specification.

> 商业许可源文 · EUROPE_PMC · [CC-BY](https://creativecommons.org/licenses/by/)

书目信息

  • 引用：Qian X, Coleman K, Jiang S, Kriz AJ, Marciano JH, Luo C, Cai C, Manam MD, Caglayan E, Lai A, Exposito-Alonso D, Otani A, Ghosh U, Shao DD, Andersen RE, Neil JE, Johnson R, LeFevre A, Hecht JL, Micali N, Sestan N, Rakic P, Miller MB, Sun L, Stringer C, Li M, Walsh CA. (2025). Spatial transcriptomics reveals human cortical layer and area specification. Nature. PMID 40369074 · PMC12328223 · DOI 10.1038/s41586-025-09010-1
  • 证据类型：PRIMARY_RESEARCH
  • 主题：rna-seq、single-cell、spatial-omics
  • 被引次数（采集时）：55
  • 原始记录：[Europe PMC](https://europepmc.org/article/MED/40369074)
  • 来源许可：[CC-BY](https://creativecommons.org/licenses/by/)

    • 作者摘要（按来源许可复用）

    The human cerebral cortex is composed of six layers and dozens of areas that are molecularly and structurally distinct 1-4 . Although single-cell transcriptomic studies have advanced the molecular characterization of human cortical development, a substantial gap exists owing to the loss of spatial context during cell dissociation 5-8 . Here we used multiplexed error-robust fluorescence in situ hybridization (MERFISH) 9 , augmented with deep-learning-based nucleus segmentation, to examine the molecular, cellular and cytoarchitectural development of the human fetal cortex with spatially resolved single-cell resolution. Our extensive spatial atlas, encompassing more than 18 million single cells, spans eight cortical areas across seven developmental time points. We uncovered the early establishment of the six-layer structure, identifiable by the laminar distribution of excitatory neuron subtypes, 3 months before the emergence of cytoarchitectural layers. Notably, we discovered two distinct modes of cortical areal specification during mid-gestation: (1) a continuous, gradual transition observed across most cortical areas along the anterior-posterior axis and (2) a discrete, abrupt boundary specifically identified between the primary (V1) and secondary (V2) visual cortices as early as gestational week 20. This sharp binary transition in V1-V2 neuronal subtypes challenges the notion that mid-gestation cortical arealization involves only gradient-like transitions 6,10 . Furthermore, integrating single-nucleus RNA sequencing with MERFISH revealed an early upregulation of synaptogenesis in V1-specific layer 4 neurons. Collectively, our findings underscore the crucial role of spatial relationships in determining the molecular specification of cortical layers and areas. This study establishes a spatially resolved single-cell analysis paradigm and paves the way for the construction of a comprehensive developmental atlas of the human brain.

    合规说明

    本页保存的是来源文献书目信息及其在 CC-BY 许可下公开的作者摘要。除去除来源 HTML 标签和规范化空白外，摘要未作内容改写。本页不代表 GeniOmics 的医学建议；原文版权、署名和许可仍归原权利人，请通过原始记录核对最新版本、更正或撤稿状态。

    Spatial transcriptomics reveals human cortical layer and area specification. · GeniOmics