{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T19:06:41Z","timestamp":1793905601275,"version":"4.8.0"},"reference-count":56,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,3,2]],"date-time":"2022-03-02T00:00:00Z","timestamp":1646179200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,3,2]],"date-time":"2022-03-02T00:00:00Z","timestamp":1646179200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sig Transduct Target Ther"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Spinal cord injury (SCI) involves diverse injury responses in different cell types in a temporally and spatially specific manner. Here, using single-cell transcriptomic analyses combined with classic anatomical, behavioral, electrophysiological analyses, we report, with single-cell resolution, temporal molecular and cellular changes in crush-injured adult mouse spinal cord. Data revealed pathological changes of 12 different major cell types, three of which infiltrated into the spinal cord at distinct times post-injury. We discovered novel microglia and astrocyte subtypes in the uninjured spinal cord, and their dynamic conversions into additional stage-specific subtypes\/states. Most dynamic changes occur at 3-days post-injury and by day-14 the second wave of microglial activation emerged, accompanied with changes in various cell types including neurons, indicative of the second round of attacks. By day-38, major cell types are still substantially deviated from uninjured states, demonstrating prolonged alterations. This study provides a comprehensive mapping of cellular\/molecular pathological changes along the temporal axis after SCI, which may facilitate the development of novel therapeutic strategies, including those targeting microglia.<\/jats:p>","DOI":"10.1038\/s41392-022-00885-4","type":"journal-article","created":{"date-parts":[[2022,3,2]],"date-time":"2022-03-02T01:02:26Z","timestamp":1646182946000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":254,"title":["Temporal and spatial cellular and molecular pathological alterations with single-cell resolution in the adult spinal cord after injury"],"prefix":"10.1038","volume":"7","author":[{"given":"Chen","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhourui","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqiang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingliang","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilong","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingfei","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihong","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunshan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiping","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runzhi","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejiao","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenmin","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongrong","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changhong","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi Eve","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liming","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,2]]},"reference":[{"key":"885_CR1","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1038\/nn.4541","volume":"20","author":"P Assinck","year":"2017","unstructured":"Assinck, P., Duncan, G. J., Hilton, B. J., Plemel, J. R. & Tetzlaff, W. Cell transplantation therapy for spinal cord injury. Nat. Neurosci. 20, 637\u2013647 (2017).","journal-title":"Nat. Neurosci."},{"key":"885_CR2","doi-asserted-by":"publisher","first-page":"13354","DOI":"10.1073\/pnas.1510194112","volume":"112","author":"Z Yang","year":"2015","unstructured":"Yang, Z. et al. NT3-chitosan elicits robust endogenous neurogenesis to enable functional recovery after spinal cord injury. Proc. Natl Acad. Sci. USA 112, 13354\u201313359 (2015).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"885_CR3","doi-asserted-by":"publisher","first-page":"2812","DOI":"10.1021\/acsnano.0c08727","volume":"15","author":"R Zhu","year":"2021","unstructured":"Zhu, R. et al. Immunomodulatory layered double hydroxide nanoparticles enable neurogenesis by targeting transforming growth factor-beta receptor 2. ACS Nano 15, 2812\u20132830 (2021).","journal-title":"ACS Nano"},{"key":"885_CR4","doi-asserted-by":"publisher","first-page":"E5595","DOI":"10.1073\/pnas.1804735115","volume":"115","author":"JS Rao","year":"2018","unstructured":"Rao, J. S. et al. NT3-chitosan enables de novo regeneration and functional recovery in monkeys after spinal cord injury. Proc. Natl Acad. Sci. USA 115, E5595\u2013E5604 (2018).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"885_CR5","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1016\/j.stem.2020.07.007","volume":"27","author":"S Ceto","year":"2020","unstructured":"Ceto, S., Sekiguchi, K. J., Takashima, Y., Nimmerjahn, A. & Tuszynski, M. H. Neural stem cell grafts form extensive synaptic networks that integrate with host circuits after spinal cord injury. Cell Stem Cell 27, 430\u2013440 (2020). e435.","journal-title":"Cell Stem Cell"},{"key":"885_CR6","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.molmed.2012.11.007","volume":"19","author":"R Shechter","year":"2013","unstructured":"Shechter, R. & Schwartz, M. CNS sterile injury: just another wound healing? Trends Mol. Med. 19, 135\u2013143 (2013).","journal-title":"Trends Mol. Med."},{"key":"885_CR7","doi-asserted-by":"publisher","first-page":"4658","DOI":"10.1523\/JNEUROSCI.0498-17.2017","volume":"37","author":"R Rust","year":"2017","unstructured":"Rust, R. & Kaiser, J. Insights into the dual role of inflammation after spinal cord injury. J. Neurosci. 37, 4658\u20134660 (2017).","journal-title":"J. Neurosci."},{"key":"885_CR8","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1177\/0963689718755778","volume":"27","author":"B Fan","year":"2018","unstructured":"Fan, B. et al. Microenvironment imbalance of spinal cord injury. Cell Transpl. 27, 853\u2013866 (2018).","journal-title":"Cell Transpl."},{"key":"885_CR9","doi-asserted-by":"publisher","first-page":"13360","DOI":"10.1073\/pnas.1510176112","volume":"112","author":"H Duan","year":"2015","unstructured":"Duan, H. et al. Transcriptome analyses reveal molecular mechanisms underlying functional recovery after spinal cord injury. Proc. Natl Acad. Sci. USA 112, 13360\u201313365 (2015).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"885_CR10","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1007\/s13238-018-0559-y","volume":"10","author":"D Luo","year":"2019","unstructured":"Luo, D. et al. Unbiased transcriptomic analyses reveal distinct effects of immune deficiency in CNS function with and without injury. Protein Cell 10, 566\u2013582 (2019).","journal-title":"Protein Cell"},{"key":"885_CR11","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1007\/s13238-017-0449-8","volume":"9","author":"B Jing","year":"2018","unstructured":"Jing, B. et al. Glycosylation of dentin matrix protein 1 is a novel key element for astrocyte maturation and BBB integrity. Protein Cell 9, 298\u2013309 (2018).","journal-title":"Protein Cell"},{"key":"885_CR12","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1038\/nature17623","volume":"532","author":"MA Anderson","year":"2016","unstructured":"Anderson, M. A. et al. Astrocyte scar formation aids central nervous system axon regeneration. Nature 532, 195\u2013200 (2016).","journal-title":"Nature"},{"key":"885_CR13","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/S0140-6736(02)07603-1","volume":"359","author":"JW McDonald","year":"2002","unstructured":"McDonald, J. W. & Sadowsky, C. Spinal-cord injury. Lancet 359, 417\u2013425 (2002).","journal-title":"Lancet"},{"key":"885_CR14","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.expneurol.2004.05.042","volume":"189","author":"JB Aimone","year":"2004","unstructured":"Aimone, J. B., Leasure, J. L., Perreau, V. M. & Thallmair, M., Christopher Reeve Paralysis Foundation Research, C. Spatial and temporal gene expression profiling of the contused rat spinal cord. Exp. Neurol. 189, 204\u2013221 (2004).","journal-title":"Exp. Neurol."},{"key":"885_CR15","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1038\/s41593-020-00795-0","volume":"24","author":"JA Blum","year":"2021","unstructured":"Blum, J. A. et al. Single-cell transcriptomic analysis of the adult mouse spinal cord reveals molecular diversity of autonomic and skeletal motor neurons. Nat. Neurosci. 24, 572\u2013583 (2021).","journal-title":"Nat. Neurosci."},{"key":"885_CR16","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1038\/s41586-020-2795-6","volume":"587","author":"Y Li","year":"2020","unstructured":"Li, Y. et al. Microglia-organized scar-free spinal cord repair in neonatal mice. Nature 587, 613\u2013618 (2020).","journal-title":"Nature"},{"key":"885_CR17","doi-asserted-by":"publisher","first-page":"210","DOI":"10.21037\/atm.2020.01.58","volume":"8","author":"C Li","year":"2020","unstructured":"Li, C., Zhu, X., Lee, C. M., Wu, Z. & Cheng, L. A mouse model of complete-crush transection spinal cord injury made by two operations. Ann. Transl. Med. 8, 210 (2020).","journal-title":"Ann. Transl. Med."},{"key":"885_CR18","doi-asserted-by":"publisher","first-page":"19578","DOI":"10.1073\/pnas.1918883117","volume":"117","author":"CM Lee","year":"2020","unstructured":"Lee, C. M. et al. Single-cell RNA-seq analysis revealed long-lasting adverse effects of tamoxifen on neurogenesis in prenatal and adult brains. Proc. Natl Acad. Sci. USA 117, 19578\u201319589 (2020).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"885_CR19","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1016\/j.neuron.2017.09.026","volume":"96","author":"YE Wu","year":"2017","unstructured":"Wu, Y. E., Pan, L., Zuo, Y., Li, X. & Hong, W. Detecting activated cell populations using single-cell RNA-seq. Neuron 96, 313\u2013329 (2017). e316.","journal-title":"Neuron"},{"key":"885_CR20","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1002\/cne.21149","volume":"500","author":"I Pineau","year":"2007","unstructured":"Pineau, I. & Lacroix, S. Proinflammatory cytokine synthesis in the injured mouse spinal cord: multiphasic expression pattern and identification of the cell types involved. J. Comp. Neurol. 500, 267\u2013285 (2007).","journal-title":"J. Comp. Neurol."},{"key":"885_CR21","doi-asserted-by":"publisher","first-page":"105187","DOI":"10.1016\/j.nbd.2020.105187","volume":"148","author":"JCT Chio","year":"2021","unstructured":"Chio, J. C. T. et al. Delayed administration of high dose human immunoglobulin G enhances recovery after traumatic cervical spinal cord injury by modulation of neuroinflammation and protection of the blood spinal cord barrier. Neurobiol. Dis. 148, 105187 (2021).","journal-title":"Neurobiol. Dis."},{"key":"885_CR22","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1016\/j.cell.2018.06.021","volume":"174","author":"A Zeisel","year":"2018","unstructured":"Zeisel, A. et al. Molecular architecture of the mouse nervous system. Cell 174, 999\u20131014 (2018). e1022.","journal-title":"Cell"},{"key":"885_CR23","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/j.conb.2019.03.003","volume":"56","author":"PJ Osseward 2nd","year":"2019","unstructured":"Osseward, P. J. 2nd & Pfaff, S. L. Cell type and circuit modules in the spinal cord. Curr. Opin. Neurobiol. 56, 175\u2013184 (2019).","journal-title":"Curr. Opin. Neurobiol."},{"key":"885_CR24","doi-asserted-by":"publisher","first-page":"2216","DOI":"10.1016\/j.celrep.2018.02.003","volume":"22","author":"A Sathyamurthy","year":"2018","unstructured":"Sathyamurthy, A. et al. Massively parallel single nucleus transcriptional profiling defines spinal cord neurons and their activity during behavior. Cell Rep. 22, 2216\u20132225 (2018).","journal-title":"Cell Rep."},{"key":"885_CR25","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1016\/j.celrep.2016.12.067","volume":"18","author":"C Chen","year":"2017","unstructured":"Chen, C., Arai, I., Satterfield, R., Young, S. M. Jr. & Jonas, P. Synaptotagmin 2 is the fast Ca(2+) sensor at a central inhibitory synapse. Cell Rep. 18, 723\u2013736 (2017).","journal-title":"Cell Rep."},{"key":"885_CR26","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/nature21029","volume":"541","author":"SA Liddelow","year":"2017","unstructured":"Liddelow, S. A. et al. Neurotoxic reactive astrocytes are induced by activated microglia. Nature 541, 481\u2013487 (2017).","journal-title":"Nature"},{"key":"885_CR27","doi-asserted-by":"publisher","first-page":"1138","DOI":"10.1126\/science.aaa1934","volume":"347","author":"A Zeisel","year":"2015","unstructured":"Zeisel, A. et al. Brain structure. Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq. Science 347, 1138\u20131142 (2015).","journal-title":"Science"},{"key":"885_CR28","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1038\/nrn3053","volume":"12","author":"S David","year":"2011","unstructured":"David, S. & Kroner, A. Repertoire of microglial and macrophage responses after spinal cord injury. Nat. Rev. Neurosci. 12, 388\u2013399 (2011).","journal-title":"Nat. Rev. Neurosci."},{"key":"885_CR29","doi-asserted-by":"publisher","first-page":"1124","DOI":"10.1080\/00207454.2017.1325884","volume":"127","author":"C Xu","year":"2017","unstructured":"Xu, C., Fu, F., Li, X. & Zhang, S. Mesenchymal stem cells maintain the microenvironment of central nervous system by regulating the polarization of macrophages\/microglia after traumatic brain injury. Int J. Neurosci. 127, 1124\u20131135 (2017).","journal-title":"Int J. Neurosci."},{"key":"885_CR30","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.neuroscience.2018.06.046","volume":"405","author":"H Thurgur","year":"2019","unstructured":"Thurgur, H. & Pinteaux, E. Microglia in the neurovascular unit: blood-brain barrier-microglia interactions after central nervous system disorders. Neuroscience 405, 55\u201367 (2019).","journal-title":"Neuroscience"},{"key":"885_CR31","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1007\/s13311-018-0630-7","volume":"15","author":"AD Gaudet","year":"2018","unstructured":"Gaudet, A. D. & Fonken, L. K. Glial cells shape pathology and repair after spinal cord injury. Neurotherapeutics 15, 554\u2013577 (2018).","journal-title":"Neurotherapeutics"},{"key":"885_CR32","doi-asserted-by":"publisher","first-page":"1320","DOI":"10.1002\/glia.22836","volume":"63","author":"AV Molofsky","year":"2015","unstructured":"Molofsky, A. V. & Deneen, B. Astrocyte development: a guide for the perplexed. Glia 63, 1320\u20131329 (2015).","journal-title":"Glia"},{"key":"885_CR33","doi-asserted-by":"publisher","first-page":"1156","DOI":"10.1016\/j.cell.2020.07.011","volume":"182","author":"A Ndoja","year":"2020","unstructured":"Ndoja, A. et al. Ubiquitin ligase COP1 suppresses neuroinflammation by degrading c\/EBPbeta in microglia. Cell 182, 1156\u20131169 (2020). e1112.","journal-title":"Cell"},{"key":"885_CR34","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04120-z","volume":"9","author":"ZH Wang","year":"2018","unstructured":"Wang, Z. H. et al. C\/EBPbeta regulates delta-secretase expression and mediates pathogenesis in mouse models of Alzheimer\u2019s disease. Nat. Commun. 9, 1784 (2018).","journal-title":"Nat. Commun."},{"key":"885_CR35","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1016\/j.celrep.2019.06.054","volume":"28","author":"ZH Wang","year":"2019","unstructured":"Wang, Z. H. et al. Deficiency in BDNF\/TrkB neurotrophic activity stimulates delta-secretase by upregulating C\/EBPbeta in Alzheimer\u2019s disease. Cell Rep. 28, 655\u2013669 (2019). e655.","journal-title":"Cell Rep."},{"key":"885_CR36","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1038\/s41586-019-1195-2","volume":"570","author":"H Mathys","year":"2019","unstructured":"Mathys, H. et al. Single-cell transcriptomic analysis of Alzheimer\u2019s disease. Nature 570, 332\u2013337 (2019).","journal-title":"Nature"},{"key":"885_CR37","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1016\/j.cell.2020.02.013","volume":"180","author":"EF Willis","year":"2020","unstructured":"Willis, E. F. et al. Repopulating microglia promote brain repair in an IL-6-dependent manner. Cell 180, 833\u2013846 (2020). e816.","journal-title":"Cell"},{"key":"885_CR38","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1016\/j.neuron.2012.03.026","volume":"74","author":"DP Schafer","year":"2012","unstructured":"Schafer, D. P. et al. Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron 74, 691\u2013705 (2012).","journal-title":"Neuron"},{"key":"885_CR39","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1016\/j.expneurol.2007.06.009","volume":"209","author":"DJ Donnelly","year":"2008","unstructured":"Donnelly, D. J. & Popovich, P. G. Inflammation and its role in neuroprotection, axonal regeneration and functional recovery after spinal cord injury. Exp. Neurol. 209, 378\u2013388 (2008).","journal-title":"Exp. Neurol."},{"key":"885_CR40","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1038\/sj.sc.3101603","volume":"42","author":"JF Ditunno","year":"2004","unstructured":"Ditunno, J. F., Little, J. W., Tessler, A. & Burns, A. S. Spinal shock revisited: a four-phase model. Spinal Cord. 42, 383\u2013395 (2004).","journal-title":"Spinal Cord."},{"key":"885_CR41","doi-asserted-by":"publisher","first-page":"E2","DOI":"10.3171\/FOC.2008.25.11.E2","volume":"25","author":"JW Rowland","year":"2008","unstructured":"Rowland, J. W., Hawryluk, G. W., Kwon, B. & Fehlings, M. G. Current status of acute spinal cord injury pathophysiology and emerging therapies: promise on the horizon. Neurosurg. Focus 25, E2 (2008).","journal-title":"Neurosurg. Focus"},{"key":"885_CR42","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1002\/mus.26379","volume":"59","author":"RWP Kissane","year":"2019","unstructured":"Kissane, R. W. P. et al. Effects of treadmill training on microvascular remodeling in the rat after spinal cord injury. Muscle Nerve 59, 370\u2013379 (2019).","journal-title":"Muscle Nerve"},{"key":"885_CR43","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.1586\/ern.11.129","volume":"11","author":"VR Edgerton","year":"2011","unstructured":"Edgerton, V. R. & Harkema, S. Epidural stimulation of the spinal cord in spinal cord injury: current status and future challenges. Expert Rev. Neurother. 11, 1351\u20131353 (2011).","journal-title":"Expert Rev. Neurother."},{"key":"885_CR44","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1006\/exnr.1999.7166","volume":"159","author":"DJ McAdoo","year":"1999","unstructured":"McAdoo, D. J., Xu, G. Y., Robak, G. & Hughes, M. G. Changes in amino acid concentrations over time and space around an impact injury and their diffusion through the rat spinal cord. Exp. Neurol. 159, 538\u2013544 (1999).","journal-title":"Exp. Neurol."},{"key":"885_CR45","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1177\/1073858409342593","volume":"16","author":"HK Kimelberg","year":"2010","unstructured":"Kimelberg, H. K. Functions of mature mammalian astrocytes: a current view. Neuroscientist 16, 79\u2013106 (2010).","journal-title":"Neuroscientist"},{"key":"885_CR46","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1016\/j.cell.2015.04.001","volume":"161","author":"Y Luo","year":"2015","unstructured":"Luo, Y. et al. Single-cell transcriptome analyses reveal signals to activate dormant neural stem cells. Cell 161, 1175\u20131186 (2015).","journal-title":"Cell"},{"key":"885_CR47","doi-asserted-by":"publisher","unstructured":"Fan, H. et al. Apoptosis-Induced Wnt2\/\u03b2-Catenin Signaling Triggers Astrocytic Dedifferentiation and Facilitates Neurogenesis in Ischemic Cortex. Res. Sq. https:\/\/doi.org\/10.21203\/rs.3.rs-41610\/v1 (2020, Preprint).","DOI":"10.21203\/rs.3.rs-41610\/v1"},{"key":"885_CR48","doi-asserted-by":"publisher","DOI":"10.1038\/srep41122","volume":"7","author":"Y Ren","year":"2017","unstructured":"Ren, Y. et al. Ependymal cell contribution to scar formation after spinal cord injury is minimal, local and dependent on direct ependymal injury. Sci. Rep. 7, 41122 (2017).","journal-title":"Sci. Rep."},{"key":"885_CR49","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1126\/science.1242576","volume":"342","author":"H Sabelstrom","year":"2013","unstructured":"Sabelstrom, H. et al. Resident neural stem cells restrict tissue damage and neuronal loss after spinal cord injury in mice. Science 342, 637\u2013640 (2013).","journal-title":"Science"},{"key":"885_CR50","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1016\/j.neuron.2018.12.010","volume":"101","author":"T Matsuda","year":"2019","unstructured":"Matsuda, T. et al. Pioneer factor NeuroD1 rearranges transcriptional and epigenetic profiles to execute microglia-neuron conversion. Neuron 101, 472\u2013485 (2019). e477.","journal-title":"Neuron"},{"key":"885_CR51","doi-asserted-by":"publisher","first-page":"7231","DOI":"10.1523\/JNEUROSCI.1709-08.2008","volume":"28","author":"JE Herrmann","year":"2008","unstructured":"Herrmann, J. E. et al. STAT3 is a critical regulator of astrogliosis and scar formation after spinal cord injury. J. Neurosci. 28, 7231\u20137243 (2008).","journal-title":"J. Neurosci."},{"key":"885_CR52","doi-asserted-by":"crossref","unstructured":"Vercelli, A. & Boido, M. In Neurobiology of Brain Disorders (eds Michael J. Zigmond, Lewis P. Rowland, & Joseph T. Coyle) 207\u2013218 (Academic Press, 2015).","DOI":"10.1016\/B978-0-12-398270-4.00015-X"},{"key":"885_CR53","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1038\/sc.2015.12","volume":"53","author":"R Nardone","year":"2015","unstructured":"Nardone, R. et al. Assessment of corticospinal excitability after traumatic spinal cord injury using MEP recruitment curves: a preliminary TMS study. Spinal Cord. 53, 534\u2013538 (2015).","journal-title":"Spinal Cord."},{"key":"885_CR54","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2003-4-5-p3","volume":"4","author":"G Dennis Jr.","year":"2003","unstructured":"Dennis, G. Jr. et al. DAVID: database for annotation, visualization, and integrated discovery. Genome Biol. 4, P3 (2003).","journal-title":"Genome Biol."},{"key":"885_CR55","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1101\/gr.1239303","volume":"13","author":"P Shannon","year":"2003","unstructured":"Shannon, P. et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 13, 2498\u20132504 (2003).","journal-title":"Genome Res."},{"key":"885_CR56","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1038\/s41586-019-0933-9","volume":"566","author":"B Pijuan-Sala","year":"2019","unstructured":"Pijuan-Sala, B. et al. A single-cell molecular map of mouse gastrulation and early organogenesis. Nature 566, 490\u2013495 (2019).","journal-title":"Nature"}],"updated-by":[{"DOI":"10.1038\/s41392-022-01012-z","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T00:00:00Z","timestamp":1652140800000}}],"container-title":["Signal Transduction and Targeted Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41392-022-00885-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41392-022-00885-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41392-022-00885-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T19:02:22Z","timestamp":1669230142000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41392-022-00885-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,2]]},"references-count":56,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["885"],"URL":"https:\/\/doi.org\/10.1038\/s41392-022-00885-4","relation":{},"ISSN":["2059-3635"],"issn-type":[{"value":"2059-3635","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,2]]},"assertion":[{"value":"23 September 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 January 2022","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 January 2022","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 March 2022","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 May 2022","order":5,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":6,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1038\/s41392-022-01012-z","URL":"https:\/\/doi.org\/10.1038\/s41392-022-01012-z","order":8,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"65"}}