{"id":331,"date":"2021-01-08T00:18:23","date_gmt":"2021-01-07T19:18:23","guid":{"rendered":"http:\/\/curesteps.org\/SCI\/?p=331"},"modified":"2021-01-08T00:18:26","modified_gmt":"2021-01-07T19:18:26","slug":"regeneration-of-functional-neurons-after-spinal-cord-injury-via-in-situ-neurod1-mediated-astrocyte-to-neuron-conversion","status":"publish","type":"post","link":"http:\/\/curesteps.org\/SCI\/regeneration-of-functional-neurons-after-spinal-cord-injury-via-in-situ-neurod1-mediated-astrocyte-to-neuron-conversion\/","title":{"rendered":"Regeneration of Functional Neurons After Spinal Cord Injury via in situ NeuroD1-Mediated Astrocyte-to-Neuron Conversion"},"content":{"rendered":"\n<p><a href=\"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2020.591883\/full?&amp;utm_source=Email_to_authors_&amp;utm_medium=Email&amp;utm_content=T1_11.5e1_author&amp;utm_campaign=Email_publication&amp;field=&amp;journalName=Frontiers_in_Cell_and_Developmental_Biology&amp;id=59\">Link<\/a><\/p>\n\n\n\n<p>Spinal cord injury (SCI) often leads to impaired motor and sensory functions, partially because the injury-induced neuronal loss cannot be easily replenished through endogenous mechanisms.\u00a0<em>In vivo<\/em>\u00a0neuronal reprogramming has emerged as a novel technology to regenerate neurons from endogenous glial cells by forced expression of neurogenic transcription factors. We have previously demonstrated successful astrocyte-to-neuron conversion in mouse brains with injury or Alzheimer&#8217;s disease by overexpressing a single neural transcription factor NeuroD1. Here we demonstrate regeneration of spinal cord neurons from reactive astrocytes after SCI through AAV NeuroD1-based gene therapy. We find that NeuroD1 converts reactive astrocytes into neurons in the dorsal horn of stab-injured spinal cord with high efficiency (~95%). Interestingly, NeuroD1-converted neurons in the dorsal horn mostly acquire glutamatergic neuronal subtype, expressing spinal cord-specific markers such as Tlx3 but not brain-specific markers such as Tbr1, suggesting that the astrocytic lineage and local microenvironment affect the cell fate after conversion. Electrophysiological recordings show that the NeuroD1-converted neurons can functionally mature and integrate into local spinal cord circuitry by displaying repetitive action potentials and spontaneous synaptic responses. We further show that NeuroD1-mediated neuronal conversion can occur in the contusive SCI model with a long delay after injury, allowing future studies to further evaluate this\u00a0<em>in vivo<\/em>\u00a0reprogramming technology for functional recovery after SCI. In conclusion, this study may suggest a paradigm shift from classical axonal regeneration to neuronal regeneration for spinal cord repair, using\u00a0<em>in vivo<\/em>\u00a0astrocyte-to-neuron conversion technology to regenerate functional new neurons in the gray matter.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Link Spinal cord injury (SCI) often leads to impaired motor and sensory functions, partially because the injury-induced neuronal loss cannot be easily replenished through endogenous mechanisms.\u00a0In vivo\u00a0neuronal reprogramming has emerged as a novel technology to regenerate neurons from endogenous glial cells by forced expression of neurogenic transcription factors. We have previously demonstrated successful astrocyte-to-neuron conversion [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4],"tags":[8],"class_list":["post-331","post","type-post","status-publish","format-standard","hentry","category-stem-cells","tag-stem-cells"],"_links":{"self":[{"href":"http:\/\/curesteps.org\/SCI\/wp-json\/wp\/v2\/posts\/331","targetHints":{"allow":["GET"]}}],"collection":[{"href":"http:\/\/curesteps.org\/SCI\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"http:\/\/curesteps.org\/SCI\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"http:\/\/curesteps.org\/SCI\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"http:\/\/curesteps.org\/SCI\/wp-json\/wp\/v2\/comments?post=331"}],"version-history":[{"count":1,"href":"http:\/\/curesteps.org\/SCI\/wp-json\/wp\/v2\/posts\/331\/revisions"}],"predecessor-version":[{"id":332,"href":"http:\/\/curesteps.org\/SCI\/wp-json\/wp\/v2\/posts\/331\/revisions\/332"}],"wp:attachment":[{"href":"http:\/\/curesteps.org\/SCI\/wp-json\/wp\/v2\/media?parent=331"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"http:\/\/curesteps.org\/SCI\/wp-json\/wp\/v2\/categories?post=331"},{"taxonomy":"post_tag","embeddable":true,"href":"http:\/\/curesteps.org\/SCI\/wp-json\/wp\/v2\/tags?post=331"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}