{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T03:23:56Z","timestamp":1787887436742,"version":"build-2784847793"},"posted":{"date-parts":[[2026,4,1]]},"group-title":"Systems Biology","reference-count":71,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Traumatic brain injury (TBI) is a major cause of mortality and long-term disability worldwide, giving rise to complex neurological complications that impact millions of individuals each year. Cellular stress and neuronal injury vary dramatically across cortical layers, vascular niches, and between the ipsilateral (injured) or contralateral (uninjured) hemispheres. There is a critical need for quantitative measures that capture the spatial distribution of injury-induced cellular changes, as well as the gene regulatory elements that drive them. Here, we developed\n                  <jats:italic>OmicGlaze<\/jats:italic>\n                  , an experimental and computational workflow for systematically profiling the spatial transcriptome and epigenome of mouse brains following mild traumatic brain injury. We established a spatial scoring system, and identified region-specific biological processes post injury, including changes in neuronal activities, cellular stress, immune response, and gliosis. Spatial assay for transposase-accessible chromatin with sequencing (Spatial ATAC-seq) generated the first epigenetic map of traumatic brain injury near single-cell resolution. Notably, we identified the Activator Protein-1 family transcription factor Atf3 as a key gene regulator of injury-induced cellular stress. Together, these spatial multi-omics analyses revealed gene regulatory network in TBI and provided a broadly applicable framework for dissecting cellular and molecular mechanisms underlying complex neurological disorders.\n                <\/jats:p>","DOI":"10.64898\/2026.03.30.715462","type":"posted-content","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T03:24:59Z","timestamp":1775100299000},"source":"Crossref","is-referenced-by-count":1,"title":["OmicGlaze: Spatial Multi-Omic Mapping of Traumatic Brain Injury"],"prefix":"10.64898","author":[{"given":"Yiheng","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam J.","family":"Neuffer","sequence":"additional","affiliation":[{"name":"Bloodworks Northwest Research Institute, Seattle, WA 98102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Wider","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA"},{"name":"Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9785-7929","authenticated-orcid":false,"given":"Sai","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"},{"name":"Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA"},{"name":"Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liam","family":"McCracken","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Sanderson","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA"},{"name":"Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-fei","family":"Dong","sequence":"additional","affiliation":[{"name":"Bloodworks Northwest Research Institute, Seattle, WA 98102, USA"},{"name":"Division of Hematology and Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9975-8086","authenticated-orcid":false,"given":"Yanxiang","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"},{"name":"Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"},{"name":"Institute of Aging, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7878-4923","authenticated-orcid":false,"given":"Yang","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA"},{"name":"Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109, USA"},{"name":"Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026040601450800000_2026.03.30.715462v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-52892-6.00001-5"},{"key":"2026040601450800000_2026.03.30.715462v1.2","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1159\/000540676","article-title":"Prevalence of Traumatic Brain Injury in the General Adult Population of the USA: A Meta-Analysis","volume":"59","year":"2024","journal-title":"Neuroepidemiology"},{"key":"2026040601450800000_2026.03.30.715462v1.3","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2010.1358"},{"key":"2026040601450800000_2026.03.30.715462v1.4","doi-asserted-by":"publisher","DOI":"10.1080\/14737159.2018.1428089"},{"key":"2026040601450800000_2026.03.30.715462v1.5","doi-asserted-by":"crossref","unstructured":"McKee CA , Lukens JR : Emerging Roles for the Immune System in Traumatic Brain Injury. Frontiers in Immunology 2016, 7.","DOI":"10.3389\/fimmu.2016.00556"},{"key":"2026040601450800000_2026.03.30.715462v1.6","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/S1474-4422(17)30371-X","article-title":"Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research","volume":"16","year":"2017","journal-title":"The Lancet Neurology"},{"key":"2026040601450800000_2026.03.30.715462v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.05.002"},{"key":"2026040601450800000_2026.03.30.715462v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/nature14590"},{"key":"2026040601450800000_2026.03.30.715462v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06812-z"},{"key":"2026040601450800000_2026.03.30.715462v1.10","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-08350-8"},{"key":"2026040601450800000_2026.03.30.715462v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2024.06.021"},{"key":"2026040601450800000_2026.03.30.715462v1.12","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06808-9"},{"key":"2026040601450800000_2026.03.30.715462v1.13","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-021-01182-1"},{"key":"2026040601450800000_2026.03.30.715462v1.14","doi-asserted-by":"publisher","DOI":"10.1126\/science.1110647"},{"key":"2026040601450800000_2026.03.30.715462v1.15","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2038"},{"key":"2026040601450800000_2026.03.30.715462v1.16","doi-asserted-by":"crossref","first-page":"115795","DOI":"10.1016\/j.celrep.2025.115795","article-title":"Widespread and cell-type-specific transcriptomic reorganization following mild traumatic brain injury","volume":"44","year":"2025","journal-title":"Cell Rep"},{"key":"2026040601450800000_2026.03.30.715462v1.17","doi-asserted-by":"crossref","unstructured":"Kounelis-Wuillaume SK , Frank AM , Goguet E , Alba C , Sukumar G , Wilkerson MD , Dalgard CL , McCabe JT , Doughty ML : A spatial gene expression signature of the mouse brain post-injury at the focal point of contusion. Cold Spring Harbor Laboratory; 2025.","DOI":"10.1101\/2025.07.21.665943"},{"key":"2026040601450800000_2026.03.30.715462v1.18","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05094-1"},{"key":"2026040601450800000_2026.03.30.715462v1.19","doi-asserted-by":"crossref","unstructured":"Pachitariu M , Rariden M , Stringer C : Cellpose-SAM: superhuman generalization for cellular segmentation. bioRxiv 2025:2025.2004.2028.651001.","DOI":"10.1101\/2025.04.28.651001"},{"key":"2026040601450800000_2026.03.30.715462v1.20","doi-asserted-by":"crossref","unstructured":"Finan JD , Vogt TE , Samei Y : Cavitation in blunt impact traumatic brain injury. Experiments in Fluids 2024, 65.","DOI":"10.1007\/s00348-024-03853-6"},{"key":"2026040601450800000_2026.03.30.715462v1.21","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1089\/neu.2008.0616","article-title":"Finite Element Analysis of Controlled Cortical Impact-Induced Cell Loss","volume":"27","year":"2010","journal-title":"Journal of Neurotrauma"},{"key":"2026040601450800000_2026.03.30.715462v1.22","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4096"},{"key":"2026040601450800000_2026.03.30.715462v1.23","unstructured":"Science AIfB: Allen Mouse Brain Atlas. 2025."},{"key":"2026040601450800000_2026.03.30.715462v1.24","doi-asserted-by":"publisher","DOI":"10.1101\/lm.2136011"},{"key":"2026040601450800000_2026.03.30.715462v1.25","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-019-0443-1"},{"key":"2026040601450800000_2026.03.30.715462v1.26","doi-asserted-by":"crossref","unstructured":"Yang T , Alessandri-Haber N , Fury W , Schaner M , Breese R , Lacroix-Fralish M , Kim J , Adler C , Macdonald LE , Atwal GS , Bai Y : AdRoit is an accurate and robust method to infer complex transcriptome composition. Communications Biology 2021, 4.","DOI":"10.1038\/s42003-021-02739-1"},{"key":"2026040601450800000_2026.03.30.715462v1.27","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1916132117"},{"key":"2026040601450800000_2026.03.30.715462v1.28","doi-asserted-by":"crossref","unstructured":"Kang G , Moo EK , Banton R , Petel OE , Harris AR : Cellular mechanisms of traumatic brain injury. npj Biological Physics and Mechanics 2025, 2.","DOI":"10.1038\/s44341-025-00020-8"},{"key":"2026040601450800000_2026.03.30.715462v1.29","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.3390\/biology12081139","article-title":"Cellular and Molecular Pathophysiology of Traumatic Brain Injury: What Have We Learned So Far?","volume":"12","year":"2023","journal-title":"Biology"},{"key":"2026040601450800000_2026.03.30.715462v1.30","doi-asserted-by":"crossref","unstructured":"Gimeno IM : Marek\u2019s Disease and Differential Diagnosis with Other Tumor Viral Diseases of Poultry. In Encyclopedia of Agriculture and Food Systems. Edited by Van Alfen NK. Oxford: Academic Press; 2014: 156\u2013171","DOI":"10.1016\/B978-0-444-52512-3.00193-5"},{"key":"2026040601450800000_2026.03.30.715462v1.31","doi-asserted-by":"crossref","unstructured":"Gage M , Gard M , Thippeswamy T : Characterization of Cortical Glial Scars in the Diisopropylfluorophosphate (DFP) Rat Model of Epilepsy. Frontiers in Cell and Developmental Biology 2022, 10.","DOI":"10.3389\/fcell.2022.867949"},{"key":"2026040601450800000_2026.03.30.715462v1.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2015.04.003"},{"key":"2026040601450800000_2026.03.30.715462v1.33","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.3390\/biomedicines12092019","article-title":"Neuropathological mRNA Expression Changes after Single Mild Traumatic Brain Injury in Pigs","volume":"12","year":"2024","journal-title":"Biomedicines"},{"key":"2026040601450800000_2026.03.30.715462v1.34","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/683909"},{"key":"2026040601450800000_2026.03.30.715462v1.35","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2014.261"},{"key":"2026040601450800000_2026.03.30.715462v1.36","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2015.4373"},{"key":"2026040601450800000_2026.03.30.715462v1.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2019.11.001"},{"key":"2026040601450800000_2026.03.30.715462v1.38","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2013.12.008"},{"key":"2026040601450800000_2026.03.30.715462v1.39","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-021-03907-6"},{"key":"2026040601450800000_2026.03.30.715462v1.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2015.02.011"},{"key":"2026040601450800000_2026.03.30.715462v1.41","doi-asserted-by":"crossref","unstructured":"Dries R , Zhu Q , Dong R , Eng C-HL , Li H , Liu K , Fu Y , Zhao T , Sarkar A , Bao F , et al: Giotto: a toolbox for integrative analysis and visualization of spatial expression data. Genome Biology 2021, 22.","DOI":"10.1186\/s13059-021-02286-2"},{"key":"2026040601450800000_2026.03.30.715462v1.42","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1213903109"},{"key":"2026040601450800000_2026.03.30.715462v1.43","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.09.025"},{"key":"2026040601450800000_2026.03.30.715462v1.44","doi-asserted-by":"crossref","unstructured":"Alam A , Thelin EP , Tajsic T , Khan DZ , Khellaf A , Patani R , Helmy A : Cellular infiltration in traumatic brain injury. Journal of Neuroinflammation 2020, 17.","DOI":"10.1186\/s12974-020-02005-x"},{"key":"2026040601450800000_2026.03.30.715462v1.45","doi-asserted-by":"publisher","DOI":"10.1038\/75556"},{"key":"2026040601450800000_2026.03.30.715462v1.46","doi-asserted-by":"crossref","first-page":"113395","DOI":"10.1016\/j.celrep.2023.113395","article-title":"Single-cell transcriptomics of human traumatic brain injury reveals activation of endogenous retroviruses in oligodendroglia","volume":"42","year":"2023","journal-title":"Cell Reports"},{"key":"2026040601450800000_2026.03.30.715462v1.47","doi-asserted-by":"crossref","first-page":"6125","DOI":"10.1038\/s41380-021-01179-x","article-title":"Disruption of NEUROD2 causes a neurodevelopmental syndrome with autistic features via cell-autonomous defects in forebrain glutamatergic neurons","volume":"26","year":"2021","journal-title":"Molecular Psychiatry"},{"key":"2026040601450800000_2026.03.30.715462v1.48","doi-asserted-by":"publisher","DOI":"10.1038\/nri2093"},{"key":"2026040601450800000_2026.03.30.715462v1.49","doi-asserted-by":"crossref","unstructured":"Shi X , Luo L , Wang J , Shen H , Li Y , Mamtilahun M , Liu C , Shi R , Lee J-H , Tian H , et al: Stroke subtype-dependent synapse elimination by reactive gliosis in mice. Nature Communications 2021, 12.","DOI":"10.1038\/s41467-021-27248-x"},{"key":"2026040601450800000_2026.03.30.715462v1.50","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1038\/nmeth.4401","article-title":"chromVAR: inferring transcription-factor-associated accessibility from single-cell epigenomic data","volume":"14","year":"2017","journal-title":"Nature Methods"},{"key":"2026040601450800000_2026.03.30.715462v1.51","doi-asserted-by":"publisher","DOI":"10.1038\/ng.263"},{"key":"2026040601450800000_2026.03.30.715462v1.52","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.113.22.3897"},{"key":"2026040601450800000_2026.03.30.715462v1.53","doi-asserted-by":"publisher","DOI":"10.1016\/j.livres.2017.08.001"},{"key":"2026040601450800000_2026.03.30.715462v1.54","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1038\/nmeth.4463","article-title":"SCENIC: single-cell regulatory network inference and clustering","volume":"14","year":"2017","journal-title":"Nature Methods"},{"key":"2026040601450800000_2026.03.30.715462v1.55","doi-asserted-by":"publisher","DOI":"10.1126\/science.1698311"},{"key":"2026040601450800000_2026.03.30.715462v1.56","doi-asserted-by":"publisher","DOI":"10.1038\/nri3344"},{"key":"2026040601450800000_2026.03.30.715462v1.57","doi-asserted-by":"crossref","first-page":"1882","DOI":"10.1016\/j.biocel.2003.10.019","article-title":"Macrophage inflammatory protein-1","volume":"36","year":"2004","journal-title":"The International Journal of Biochemistry & Cell Biology"},{"key":"2026040601450800000_2026.03.30.715462v1.58","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.bbamcr.2018.09.009","article-title":"Induction of early growth response gene 1 (EGR1) by endoplasmic reticulum stress is mediated by the extracellular regulated kinase (ERK) arm of the MAPK pathways","volume":"1866","year":"2019","journal-title":"Biochimica et Biophysica Acta (BBA) - Molecular Cell Research"},{"key":"2026040601450800000_2026.03.30.715462v1.59","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.7.982"},{"key":"2026040601450800000_2026.03.30.715462v1.60","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/s11011-012-9309-7","article-title":"Developmental traumatic brain injury decreased brain derived neurotrophic factor expression late after injury","volume":"27","year":"2012","journal-title":"Metabolic Brain Disease"},{"key":"2026040601450800000_2026.03.30.715462v1.61","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1186\/ar2338","article-title":"Activator protein 1 (Fos\/Jun) functions in inflammatory bone and skin disease","volume":"10","year":"2007","journal-title":"Arthritis Research & Therapy"},{"key":"2026040601450800000_2026.03.30.715462v1.62","doi-asserted-by":"crossref","unstructured":"Sampieri L , Di Giusto P , Alvarez C : CREB3 Transcription Factors: ER-Golgi Stress Transducers as Hubs for Cellular Homeostasis. Frontiers in Cell and Developmental Biology 2019, 7.","DOI":"10.3389\/fcell.2019.00123"},{"key":"2026040601450800000_2026.03.30.715462v1.63","doi-asserted-by":"publisher","DOI":"10.1002\/stem.35"},{"key":"2026040601450800000_2026.03.30.715462v1.64","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.122079599"},{"key":"2026040601450800000_2026.03.30.715462v1.65","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"2026040601450800000_2026.03.30.715462v1.66","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-05795-1"},{"key":"2026040601450800000_2026.03.30.715462v1.67","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1182\/blood.2020007364","article-title":"Conformation-dependent blockage of activated VWF improves outcomes of traumatic brain injury in mice","volume":"137","year":"2021","journal-title":"Blood"},{"key":"2026040601450800000_2026.03.30.715462v1.68","doi-asserted-by":"publisher","DOI":"10.1089\/neu.1998.15.599"},{"key":"2026040601450800000_2026.03.30.715462v1.69","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1089\/genbio.2023.0044","article-title":"Improved Cell-Type Identification and Comprehensive Mapping of Regulatory Features with Spatial Epigenomics 96-Channel Microfluidic Platform","volume":"2","year":"2023","journal-title":"GEN Biotechnology"},{"key":"2026040601450800000_2026.03.30.715462v1.70","doi-asserted-by":"crossref","unstructured":"Barnett J , Silverman J , Wetzel M , Rao P , Sotudeh N , Wang L : AtlasXbrowser enables spatial multi-omics data analysis through the precise determination of the region of interest. Cold Spring Harbor Laboratory; 2022.","DOI":"10.1101\/2022.05.11.491526"},{"key":"2026040601450800000_2026.03.30.715462v1.71","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-023-02139-9"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.03.30.715462","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T08:45:48Z","timestamp":1775465148000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.03.30.715462"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,1]]},"references-count":71,"URL":"https:\/\/doi.org\/10.64898\/2026.03.30.715462","relation":{},"subject":[],"published":{"date-parts":[[2026,4,1]]},"subtype":"preprint"}}