Spatial profiling of the interplay between cell type- and vision- dependent transcriptomic programs in the visual cortex

• 成果类型: Article
• 署名作者: Xie, Fangming; Jain, Saumya; Xu, Runzhe; Butrus, Salwan; Tan, Zhiqun; Xu, Xiangmin; Shekhar, Karthik; Zipursky, S. Lawrence
• 署名单位: University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; University System of Georgia; Georgia Institute of Technology; University of California System; University of California Berkeley; University of California System; University of California Berkeley; University of California System; University of California Irvine; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11773
• DOI: 10.1073/pnas.2421022122
• 发表日期: 2025-02-18
• 关键词: plasticity; experience; circuitry; responses; neurons; atlas

摘要

How early sensory experience during critical periods of postnatal life affects the organization of the mammalian neocortex at the resolution of neuronal cell types is poorly understood. We previously reported that the functional and molecular profiles of layer 2/3 (L2/3) cell types in the primary visual cortex (V1) are vision- dependent [S. Cheng et al., Cell 185, 311-327.e24 (2022)]. Here, we characterize the spatial organization of L2/3 cell types with and without visual experience. Spatial transcriptomic profiling based on 500 genes recapitulates the zonation of L2/3 cell types along the pial-ventricular axis in V1. By applying multitasking theory, we suggest that the spatial zonation of L2/3 cell types is linked to the continuous nature of their gene expression profiles, which can be represented as a 2D manifold bounded by three archetypal cell types. By comparing normally reared and dark reared L2/3 cells, we show that visual deprivation- induced transcriptomic changes comprise two independent gene programs. The first, induced specifically in the visual cortex, includes immediate- early genes and genes associated with metabolic processes. It manifests as a change in cell state that is orthogonal to cell- type- specific gene expression programs. By contrast, the second program impacts L2/3 cell- type identity, regulating a subset of cell- type- specific genes and shifting the distribution of cells within the L2/3 cell- type manifold. Through an integrated analysis of spatial transcriptomics with single- nucleus RNA-seq data, we describe how vision patterns cortical L2/3 cell types during the critical period.