{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T11:41:43Z","timestamp":1792496503313,"version":"4.5.0"},"reference-count":42,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:00:00Z","timestamp":1792108800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:00:00Z","timestamp":1792108800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:00:00Z","timestamp":1792108800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Brain Science and Brain-like Intelligence Technology\u2013National Science and Technology Major Project","award":["2022ZD0207200"],"award-info":[{"award-number":["2022ZD0207200"]}]},{"name":"National Natural Science Foundation of China","award":["82621102"],"award-info":[{"award-number":["82621102"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"award":["82621102"],"award-info":[{"award-number":["82621102"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Brain Science and Brain-like Intelligence Technology\u2013National Science and Technology Major Project","award":["2022ZD0204700"],"award-info":[{"award-number":["2022ZD0204700"]}]},{"name":"National Natural Science Foundation of China","award":["32571128"],"award-info":[{"award-number":["32571128"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"award":["32571128"],"award-info":[{"award-number":["32571128"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Natural Science Foundation of China","award":["323B2030"],"award-info":[{"award-number":["323B2030"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"award":["323B2030"],"award-info":[{"award-number":["323B2030"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Natural Science Foundation of China","award":["325B2039"],"award-info":[{"award-number":["325B2039"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"award":["325B2039"],"award-info":[{"award-number":["325B2039"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"The Fellowship of China National Postdoctoral Program for Innovative Talents","award":["BX20250132"],"award-info":[{"award-number":["BX20250132"]}]},{"name":"China Postdoctoral Science Foundation","award":["2025M782569"],"award-info":[{"award-number":["2025M782569"]}],"id":[{"id":"https:\/\/ror.org\/0426zh255","id-type":"ROR","asserted-by":"crossref"}]},{"award":["2025M782569"],"award-info":[{"award-number":["2025M782569"]}],"id":[{"id":"https:\/\/ror.org\/0426zh255","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Shanghai Pilot Program for Basic Research","award":["21TQ014"],"award-info":[{"award-number":["21TQ014"]}]},{"name":"Changping Laboratory","award":["2025B-07-18"],"award-info":[{"award-number":["2025B-07-18"]}],"id":[{"id":"https:\/\/ror.org\/04kf84k17","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Lin Gang Laboratory","award":["LGL-8998-02"],"award-info":[{"award-number":["LGL-8998-02"]}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>In situ glia-to-neuron conversion induced by a single transcription factor is a promising regenerative strategy for treating central nervous system injuries and neurodegenerative diseases. Previous studies reported that NeuroD1 can induce microglia-to-neuron cross-lineage conversion and improve recovery after brain injury. However, these findings remain controversial. To examine the ability of NeuroD1 in inducing microglia-to-neuron conversion, we employed virus-free genetic lineage tracing systems in mice to specifically induce NeuroD1 expression in microglia and track the cell fate of NeuroD1-expressing cells at multiple timepoints. Meanwhile, we longitudinally monitored NeuroD1-expressing microglia via two-photon imaging and characterized their transcriptional profile by single-cell RNA sequencing. All observations across these methods revealed that NeuroD1-expressing cells retained their microglia identity and cannot convert into neurons, under either physiological and injury conditions. Instead, sustained expression of NeuroD1 induced microglial apoptosis in vivo. Collectively, our findings provide strong evidence that NeuroD1 is not sufficient to induce microglia-to-neuron conversion. This study further highlights the importance of rigorous lineage tracing and cell fate mapping strategies for validating in situ glia-to-neuron conversion.<\/jats:p>","DOI":"10.7554\/elife.112083","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T16:30:14Z","timestamp":1786638614000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.112083","source":"Crossref","is-referenced-by-count":0,"title":["In vivo virus-free lineage tracing and live imaging reveal that NeuroD1 does not reprogram microglia into neurons"],"prefix":"10.7554","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5156-8518","authenticated-orcid":true,"given":"Xiaoyu","family":"Li","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013q1eq08","id-type":"ROR","asserted-by":"publisher"}],"name":"National Children\u2019s Medical Center, Children\u2019s Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan SANS Neuroscience Center, Fudan University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0143-1710","authenticated-orcid":true,"given":"Yuxin","family":"Li","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013q1eq08","id-type":"ROR","asserted-by":"publisher"}],"name":"National Children\u2019s Medical Center, Children\u2019s Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan SANS Neuroscience Center, Fudan University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Yue","family":"Cao","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013q1eq08","id-type":"ROR","asserted-by":"publisher"}],"name":"National Children\u2019s Medical Center, Children\u2019s Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan SANS Neuroscience Center, Fudan University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9832-1360","authenticated-orcid":true,"given":"Niewen","family":"Hu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013q1eq08","id-type":"ROR","asserted-by":"publisher"}],"name":"National Children\u2019s Medical Center, Children\u2019s Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan SANS Neuroscience Center, Fudan University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6945-9248","authenticated-orcid":true,"given":"Baozhi","family":"Yang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013q1eq08","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Neurology, Zhongshan Hospital, Laboratory Animal Center, Fudan University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8740-6629","authenticated-orcid":true,"given":"Pei","family":"Ouyang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013q1eq08","id-type":"ROR","asserted-by":"publisher"}],"name":"National Children\u2019s Medical Center, Children\u2019s Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan SANS Neuroscience Center, Fudan University","place":["Shanghai, China"]},{"id":[{"id":"https:\/\/ror.org\/013q1eq08","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Neurology, Zhongshan Hospital, Laboratory Animal Center, Fudan University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Yuxiao","family":"Jin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013q1eq08","id-type":"ROR","asserted-by":"publisher"}],"name":"National Children\u2019s Medical Center, Children\u2019s Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan SANS Neuroscience Center, Fudan University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Shuai","family":"Gao","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013q1eq08","id-type":"ROR","asserted-by":"publisher"}],"name":"National Children\u2019s Medical Center, Children\u2019s Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan SANS Neuroscience Center, Fudan University","place":["Shanghai, China"]},{"id":[{"id":"https:\/\/ror.org\/013q1eq08","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Neurology, Zhongshan Hospital, Laboratory Animal Center, Fudan University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Li","family":"Cao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Neurobiology, Ministry of Education, Navy Military Medical University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"resources","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4183-5939","authenticated-orcid":true,"given":"Bo","family":"Peng","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013q1eq08","id-type":"ROR","asserted-by":"publisher"}],"name":"National Children\u2019s Medical Center, Children\u2019s Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan SANS Neuroscience Center, Fudan University","place":["Shanghai, China"]},{"id":[{"id":"https:\/\/ror.org\/013q1eq08","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Neurosurgery, Huashan Hospital, Fudan University","place":["Shanghai, China"]},{"id":[{"id":"https:\/\/ror.org\/013q1eq08","id-type":"ROR","asserted-by":"publisher"}],"name":"MOE Innovative Center for New Drug Development of Immune Inflammatory Diseases, Shanghai Key Laboratory of Gene Editing and Cell Therapy for Rare Diseases, Fudan University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"corresponding-author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5292-2056","authenticated-orcid":true,"given":"Yanxia","family":"Rao","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013q1eq08","id-type":"ROR","asserted-by":"publisher"}],"name":"National Children\u2019s Medical Center, Children\u2019s Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan SANS Neuroscience Center, Fudan University","place":["Shanghai, China"]},{"id":[{"id":"https:\/\/ror.org\/013q1eq08","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Neurology, Zhongshan Hospital, Laboratory Animal Center, Fudan University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"corresponding-author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"4374","published-online":{"date-parts":[[2026,10,16]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.113660","type":"journal-article","article-title":"A comparative evaluation of the strengths and potential caveats of the microglial inducible CreER mouse models","volume":"43","author":"Bedolla","year":"2024","journal-title":"Cell Reports"},{"key":"bib2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2504697122","type":"journal-article","article-title":"ALKBH5 demethylates the m6A modification of SOCS3 in microglia\/macrophages and alleviates neuroinflammation after brain injury","volume":"122","author":"Cai","year":"2025","journal-title":"PNAS"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1016\/j.stemcr.2014.05.020","type":"journal-article","article-title":"Generation of induced neuronal cells by the single reprogramming factor ASCL1","volume":"3","author":"Chanda","year":"2014","journal-title":"Stem Cell Reports"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1002\/cbf.3740","type":"journal-article","article-title":"ATG5: A central autophagy regulator implicated in various human diseases","volume":"40","author":"Changotra","year":"2022","journal-title":"Cell Biochemistry and Function"},{"key":"bib5","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-018-0018-5","type":"journal-article","article-title":"The independence of and associations among apoptosis, autophagy, and necrosis","volume":"3","author":"Chen","year":"2018","journal-title":"Signal Transduction and Targeted Therapy"},{"key":"bib6","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.75636","type":"journal-article","article-title":"Repressing PTBP1 fails to convert reactive astrocytes to dopaminergic neurons in a 6-hydroxydopamine mouse model of Parkinson\u2019s disease","volume":"11","author":"Chen","year":"2022","journal-title":"eLife"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1016\/j.stem.2013.12.001","type":"journal-article","article-title":"In vivo direct reprogramming of reactive glial cells into functional neurons after brain injury and in an Alzheimer\u2019s disease model","volume":"14","author":"Guo","year":"2014","journal-title":"Cell Stem Cell"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"7309","DOI":"10.1523\/JNEUROSCI.1060-22.2022","type":"journal-article","article-title":"Downregulating PTBP1 fails to convert astrocytes into hippocampal neurons and to alleviate symptoms in alzheimer\u2019s mouse models","volume":"42","author":"Guo","year":"2022","journal-title":"The Journal of Neuroscience"},{"key":"bib9","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-46956-8","type":"journal-article","article-title":"Cell-fate conversion of intestinal cells in adult Drosophila midgut by depleting a single transcription factor","volume":"15","author":"Guo","year":"2024","journal-title":"Nature Communications"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"1000","DOI":"10.1016\/j.stemcr.2014.10.007","type":"journal-article","article-title":"Sox2-mediated conversion of NG2 glia into induced neurons in the injured adult cerebral cortex","volume":"3","author":"Heinrich","year":"2014","journal-title":"Stem Cell Reports"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1038\/nn828","type":"journal-article","article-title":"Glial cells generate neurons: the role of the transcription factor Pax6","volume":"5","author":"Heins","year":"2002","journal-title":"Nature Neuroscience"},{"key":"bib12","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110849","type":"journal-article","article-title":"Genetic loss of function of Ptbp1 does not induce glia-to-neuron conversion in retina","volume":"39","author":"Hoang","year":"2022","journal-title":"Cell Reports"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"E1","DOI":"10.1038\/s41586-023-06066-9","type":"journal-article","article-title":"Ptbp1 deletion does not induce astrocyte-to-neuron conversion","volume":"618","author":"Hoang","year":"2023","journal-title":"Nature"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1038\/s41593-018-0090-8","type":"journal-article","article-title":"Repopulated microglia are solely derived from the proliferation of residual microglia after acute depletion","volume":"21","author":"Huang","year":"2018","journal-title":"Nature Neuroscience"},{"key":"bib15","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2307972120","type":"journal-article","article-title":"Direct neuronal conversion of microglia\/macrophages reinstates neurological function after stroke","volume":"120","author":"Irie","year":"2023","journal-title":"PNAS"},{"key":"bib16","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0448-18.2019","type":"journal-article","article-title":"Tmem119-EGFP and Tmem119-CreERT2 transgenic mice for labeling and manipulating microglia","volume":"6","author":"Kaiser","year":"2019","journal-title":"eNeuro"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1016\/j.ymthe.2022.01.028","type":"journal-article","article-title":"Limited astrocyte-to-neuron conversion in the mouse brain using NeuroD1 overexpression","volume":"30","author":"Leib","year":"2022","journal-title":"Molecular Therapy"},{"key":"bib18","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-55292-7","type":"journal-article","article-title":"Intestinal Neurod1 expression impairs paneth cell differentiation and promotes enteroendocrine lineage specification","volume":"9","author":"Li","year":"2019","journal-title":"Scientific Reports"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"1288","DOI":"10.1038\/s43587-023-00479-x","type":"journal-article","article-title":"Transcriptional and epigenetic decoding of the microglial aging process","volume":"3","author":"Li","year":"2023","journal-title":"Nature Aging"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1016\/j.neuron.2018.12.010","type":"journal-article","article-title":"Pioneer factor neuroD1 rearranges transcriptional and epigenetic profiles to execute microglia-neuron conversion","volume":"101","author":"Matsuda","year":"2019","journal-title":"Neuron"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"3912","DOI":"10.1016\/j.neuron.2021.11.012","type":"journal-article","article-title":"Clarifying the ability of NeuroD1 to convert mouse microglia into neurons","volume":"109","author":"Matsuda","year":"2021","journal-title":"Neuron"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"1164","DOI":"10.1038\/ncb2843","type":"journal-article","article-title":"In vivo reprogramming of astrocytes to neuroblasts in the adult brain","volume":"15","author":"Niu","year":"2013","journal-title":"Nature Cell Biology"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1016\/j.stemcr.2015.03.006","type":"journal-article","article-title":"SOX2 reprograms resident astrocytes into neural progenitors in the adult brain","volume":"4","author":"Niu","year":"2015","journal-title":"Stem Cell Reports"},{"key":"bib24","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-2724-5","type":"journal-article","article-title":"Autophagy as a modulator of cell death machinery","volume":"11","author":"Noguchi","year":"2020","journal-title":"Cell Death & Disease"},{"key":"bib25","doi-asserted-by":"publisher","DOI":"10.1186\/1475-925X-2-13","type":"journal-article","article-title":"ScanImage: flexible software for operating laser scanning microscopes","volume":"2","author":"Pologruto","year":"2003","journal-title":"Biomedical Engineering Online"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1038\/s41586-020-2388-4","type":"journal-article","article-title":"Reversing a model of Parkinson\u2019s disease with in situ converted nigral neurons","volume":"582","author":"Qian","year":"2020","journal-title":"Nature"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"4094","DOI":"10.1016\/j.neuron.2021.11.008","type":"journal-article","article-title":"NeuroD1 induces microglial apoptosis and cannot induce microglia-to-neuron cross-lineage reprogramming","volume":"109","author":"Rao","year":"2021","journal-title":"Neuron"},{"key":"bib28","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-022-00912-z","type":"journal-article","article-title":"Failure of observing NeuroD1-induced microglia-to-neuron conversion in vitro is not attributed to the low NeuroD1 expression level","volume":"15","author":"Rao","year":"2022","journal-title":"Molecular Brain"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"1807","DOI":"10.1016\/j.stem.2025.10.014","type":"journal-article","article-title":"The evolution of microglia replacement: A new paradigm for CNS disease therapy","volume":"32","author":"Rao","year":"2025","journal-title":"Cell Stem Cell"},{"key":"bib30","doi-asserted-by":"publisher","DOI":"10.1038\/mtm.2016.26","type":"journal-article","article-title":"Microglia-specific targeting by novel capsid-modified AAV6 vectors","volume":"3","author":"Rosario","year":"2016","journal-title":"Molecular Therapy. Methods & Clinical Development"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"988","DOI":"10.1016\/j.ymthe.2022.01.029","type":"journal-article","article-title":"Lineage tracing: The gold standard to claim direct reprogramming in vivo","volume":"30","author":"Svendsen","year":"2022","journal-title":"Molecular Therapy"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1016\/j.stem.2021.02.009","type":"journal-article","article-title":"In vivo reprogramming of NG2 glia enables adult neurogenesis and functional recovery following spinal cord injury","volume":"28","author":"Tai","year":"2021","journal-title":"Cell Stem Cell"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"18150","DOI":"10.1073\/pnas.1210150109","type":"journal-article","article-title":"Microglial repopulation model reveals a robust homeostatic process for replacing CNS myeloid cells","volume":"109","author":"Varvel","year":"2012","journal-title":"PNAS"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"5465","DOI":"10.1016\/j.cell.2021.09.005","type":"journal-article","article-title":"Revisiting astrocyte to neuron conversion with lineage tracing in vivo","volume":"184","author":"Wang","year":"2021","journal-title":"Cell"},{"key":"bib35","doi-asserted-by":"publisher","DOI":"10.1126\/science.adr1015","type":"journal-article","article-title":"Microglia replacement halts the progression of microgliopathy in mice and humans","volume":"389","author":"Wu","year":"2025","journal-title":"Science"},{"key":"bib36","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110960","type":"journal-article","article-title":"Critical examination of Ptbp1-mediated glia-to-neuron conversion in the mouse retina","volume":"39","author":"Xie","year":"2022","journal-title":"Cell Reports"},{"key":"bib37","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2023.104531","type":"journal-article","article-title":"New AAV tools fail to detect Neurod1-mediated neuronal conversion of M\u00fcller glia and astrocytes in vivo","volume":"90","author":"Xie","year":"2023","journal-title":"EBioMedicine"},{"key":"bib38","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108041","type":"journal-article","article-title":"Efficient strategies for microglia replacement in the central nervous system","volume":"32","author":"Xu","year":"2020","journal-title":"Cell Reports"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1038\/s41434-023-00382-5","type":"journal-article","article-title":"Ptbp1 knockdown failed to induce astrocytes to neurons in vivo","volume":"30","author":"Yang","year":"2023","journal-title":"Gene Therapy"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.immuni.2012.12.001","type":"journal-article","article-title":"Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis","volume":"38","author":"Yona","year":"2013","journal-title":"Immunity"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1016\/j.cell.2020.03.024","type":"journal-article","article-title":"Glia-to-neuron conversion by CRISPR-CasRx alleviates symptoms of neurological disease in mice","volume":"181","author":"Zhou","year":"2020","journal-title":"Cell"},{"key":"dataset1","type":"dataset","article-title":"scRNA-seq data from normal microglia and NeuroD1-overexpressing microglia under both normal and TBI conditions","volume-title":"NCBI Gene Expression Omnibus","author":"Li","year":"2026","unstructured":"Li X, Rao Y, Peng B. 2026. scRNA-seq data from normal microglia and NeuroD1-overexpressing microglia under both normal and TBI conditions. NCBI Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE277222. GSE277222."}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/112083\/elife-112083-v3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/112083\/elife-112083-v3.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/112083","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T11:00:46Z","timestamp":1792494046000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/112083"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,16]]},"references-count":42,"alternative-id":["10.7554\/eLife.112083"],"URL":"https:\/\/doi.org\/10.7554\/elife.112083","archive":["CLOCKSS"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.64898\/2026.06.08.730780","asserted-by":"subject"}],"is-same-as":[{"id-type":"doi","id":"10.7554\/eLife.112083.3","asserted-by":"subject"}],"is-version-of":[{"id-type":"doi","id":"10.7554\/eLife.112083.1","asserted-by":"subject"},{"id-type":"doi","id":"10.7554\/eLife.112083.2","asserted-by":"subject"}],"is-supplemented-by":[{"id-type":"accession","id":"GSE277222","asserted-by":"subject"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,16]]},"assertion":[{"value":"single anonymised","name":"peer_review_transparency","label":"Peer review transparency","group":{"name":"peer_review_taxonomy"}},{"value":"other reviewer(s), editor","name":"peer_review_interaction","label":"Peer review interaction","group":{"name":"peer_review_taxonomy"}},{"value":"review summaries, review reports, author\/editor communication, reviewer identities reviewer opt in, editor identities","name":"peer_review_published","label":"Peer review published","group":{"name":"peer_review_taxonomy"}},{"value":"open (sign in with ORCID iD required)","name":"post_publication_commenting","label":"Post publication commenting","group":{"name":"post_publication_commenting"}}],"article-number":"RP112083"}}