{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T22:29:08Z","timestamp":1787005748971,"version":"build-2736575974"},"reference-count":61,"publisher":"National Academy of Sciences","issue":"7","license":[{"start":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T00:00:00Z","timestamp":1739404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000888","name":"W. M. Keck Foundation","doi-asserted-by":"publisher","award":["xx"],"award-info":[{"award-number":["xx"]}],"id":[{"id":"10.13039\/100000888","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,2,18]]},"abstract":"<jats:p>\n                    How early sensory experience during \u201ccritical periods\u201d 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\n                    <jats:italic>et al.<\/jats:italic>\n                    ,\n                    <jats:italic>Cell<\/jats:italic>\n                    <jats:bold>185<\/jats:bold>\n                    , 311\u2013327.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\u2013ventricular 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.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2421022122","type":"journal-article","created":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T14:19:06Z","timestamp":1739456346000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":12,"title":["Spatial profiling of the interplay between cell type- and vision-dependent transcriptomic programs in the visual cortex"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5232-1648","authenticated-orcid":false,"given":"Fangming","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Biological Chemistry, David Geffen School of Medicine, University of California","place":["Los Angeles"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saumya","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, David Geffen School of Medicine, University of California","place":["Los Angeles"]},{"name":"School of Biological Sciences, Georgia Institute of Technology","place":["Atlanta"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runzhe","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, David Geffen School of Medicine, University of California","place":["Los Angeles"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salwan","family":"Butrus","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering, University of California","place":["Berkeley"]},{"name":"Helen Wills Neuroscience Institute, University of California","place":["Berkeley"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2235-4577","authenticated-orcid":false,"given":"Zhiqun","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, Center for Neural Circuit Mapping, Institute for Memory Impairments and Neurological Disorders, University of California","place":["Irvine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangmin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, Center for Neural Circuit Mapping, Institute for Memory Impairments and Neurological Disorders, University of California","place":["Irvine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karthik","family":"Shekhar","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering, University of California","place":["Berkeley"]},{"name":"Helen Wills Neuroscience Institute, University of California","place":["Berkeley"]},{"name":"Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory","place":["Berkeley"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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