{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:59:52Z","timestamp":1792112392695,"version":"4.4.0"},"reference-count":72,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"30","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,7,25]]},"abstract":"<jats:p>\n            In vivo conversion of nonneuronal cells into neurons is a proposed strategy to replace neurons lost to CNS injury or disease. Glia-to-neuron trans-differentiation by viral vector\u2013mediated GFAP mini-promoter\u2013driven NeuroD1 remains hotly debated. Developing inducible, lineage-traceable transgenic mice, we find that astrocyte-to-neuron conversion is restricted to a specific time window within the lesion core of injured spinal cord and brain. Spatiotemporal lineage-mapping combined with single-cell transcriptomics reveals that ectopic NeuroD1 induces astrocyte-to-neuron conversion specifically in lesion cores via transit-amplifying OLIG2\n            <jats:sup>+<\/jats:sup>\n            progenitors during early injury phase, but not in late phases or in nonreactive astrocytes. Neither a loss-of-function NeuroD1 mutant nor stemness-reprogramming factor SOX2 induces astrocyte-to-neuron conversion. However, contrary to previous reports, the neuronal-like cells generated by NeuroD1 lack mature neuroelectrical properties, limiting their functional integration into neural circuits. Together, our findings establish a spatiotemporal framework for NeuroD1-driven glia-to-neuron conversion, revealing a mechanistic shift from direct astrocyte conversion toward transit-amplifying intermediates and highlighting the functional immaturity of NeuroD1-converted neurons.\n          <\/jats:p>","DOI":"10.1126\/sciadv.adw9296","type":"journal-article","created":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T17:58:38Z","timestamp":1753466318000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":10,"title":["Neurons derived from NeuroD1-expressing astrocytes transition through transit-amplifying intermediates but lack functional maturity"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4884-4419","authenticated-orcid":true,"given":"Fangbing","family":"Chen","sequence":"first","affiliation":[{"name":"Institute of Pediatrics, Children\u2019s Hospital of Fudan University, Shanghai 201102, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8720-5591","authenticated-orcid":true,"given":"Xi","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute for Translational Brain Research, Department of Neurosurgery, Jinshan Hospital, Fudan University, Shanghai 200433, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5366-0143","authenticated-orcid":true,"given":"Xiaowen","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Brain Tumor Center, Division of Experimental Hematology and Cancer Biology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqing","family":"Chen","sequence":"additional","affiliation":[{"name":"Departments of Neonatology, International Peace Maternity and Children Hospital of China Welfare Institution, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2486-270X","authenticated-orcid":true,"given":"Eva","family":"Nicholson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Brain Tumor Center, Division of Experimental Hematology and Cancer Biology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6175-3765","authenticated-orcid":true,"given":"Kaiyi","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Pediatrics, Children\u2019s Hospital of Fudan University, Shanghai 201102, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4781-3941","authenticated-orcid":true,"given":"Huiyao","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine, Children\u2019s Hospital of Fudan University, Shanghai 201102, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifeng","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Pediatrics, Children\u2019s Hospital of Fudan University, Shanghai 201102, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2834-2876","authenticated-orcid":true,"given":"Yousheng","family":"Shu","sequence":"additional","affiliation":[{"name":"Institute for Translational Brain Research, Department of Neurology, Huashan Hospital, Fudan University, Shanghai 200031, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8956-7238","authenticated-orcid":true,"given":"Wenhao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defects, Children\u2019s Hospital of Fudan University, Shanghai 201102, China."},{"name":"Division of Neonatology and Center for Newborn Care, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 511400, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3567-0058","authenticated-orcid":true,"given":"Carol J.","family":"Schuurmans","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute, Department of Biochemistry, University of Toronto, Toronto, ON, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6846-9014","authenticated-orcid":true,"given":"Q. 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