{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T19:41:28Z","timestamp":1786650088417,"version":"build-2736575974"},"reference-count":56,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","license":[{"start":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T00:00:00Z","timestamp":1720569600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:p>JOURNAL\/nrgr\/04.03\/01300535-202511000-00030\/figure1\/v\/2026-04-24T022020Z\/r\/image-tiff<\/jats:p>\n                  <jats:p>\n                    We previously demonstrated that inhibiting neural stem cells necroptosis enhances functional recovery after spinal cord injury. While exosomes are recognized as playing a pivotal role in neural stem cells exocrine function, their precise function in spinal cord injury remains unclear. To investigate the role of exosomes generated following neural stem cells necroptosis after spinal cord injury, we conducted single-cell RNA sequencing and validated that neural stem cells originate from ependymal cells and undergo necroptosis in response to spinal cord injury. Subsequently, we established an\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    necroptosis model using neural stem cells isolated from embryonic mice aged 16\u201317 days and extracted exosomes. The results showed that necroptosis did not significantly impact the fundamental characteristics or number of exosomes. Transcriptome sequencing of exosomes in necroptosis group identified 108 differentially expressed messenger RNAs, 104 long non-coding RNAs, 720 circular RNAs, and 14 microRNAs compared with the control group. Construction of a competing endogenous RNA network identified the following hub genes: tuberous sclerosis 2 (\n                    <jats:italic toggle=\"yes\">Tsc2<\/jats:italic>\n                    ), solute carrier family 16 member 3 (\n                    <jats:italic toggle=\"yes\">Slc16a3<\/jats:italic>\n                    ), and forkhead box protein P1 (\n                    <jats:italic toggle=\"yes\">Foxp1<\/jats:italic>\n                    ). Notably, a significant elevation in TSC2 expression was observed in spinal cord tissues following spinal cord injury. TSC2-positive cells were localized around SRY-box transcription factor 2\u2013positive cells within the injury zone. Furthermore,\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    analysis revealed increased TSC2 expression in exosomal receptor cells compared with other cells. Further assessment of cellular communication following spinal cord injury showed that\n                    <jats:italic toggle=\"yes\">Tsc2<\/jats:italic>\n                    was involved in ependymal cellular communication at 1 and 3 days post-injury through the epidermal growth factor and midkine signaling pathways. In addition,\n                    <jats:italic toggle=\"yes\">Slc16a3<\/jats:italic>\n                    participated in cellular communication in ependymal cells at 7 days post-injury via the vascular endothelial growth factor and macrophage migration inhibitory factor signaling pathways. Collectively, these findings confirm that exosomes derived from neural stem cells undergoing necroptosis play an important role in cellular communication after spinal cord injury and induce TSC2 upregulation in recipient cells.\n                  <\/jats:p>","DOI":"10.4103\/nrr.nrr-d-24-00068","type":"journal-article","created":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T04:11:16Z","timestamp":1720757476000},"page":"3273-3286","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":9,"title":["Exosomes originating from neural stem cells undergoing necroptosis participate in cellular communication by inducing TSC2 upregulation of recipient cells following spinal cord injury"],"prefix":"10.4103","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7253-0495","authenticated-orcid":false,"given":"Shiming","family":"Li","sequence":"first","affiliation":[{"name":"Shenzhen Key Laboratory of Bone Tissue Repair and Translational Research, Department of Orthopedic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfeng","family":"Li","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Bone Tissue Repair and Translational Research, Department of Orthopedic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoliang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Traumatology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3332-4453","authenticated-orcid":false,"given":"Penghui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Bone Tissue Repair and Translational Research, Department of Orthopedic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9846-5655","authenticated-orcid":false,"given":"Kuileung","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4576-2311","authenticated-orcid":false,"given":"Ningning","family":"Chen","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Bone Tissue Repair and Translational Research, Department of Orthopedic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoyu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2024,7,10]]},"reference":[{"key":"R1-20260424","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1038\/s41590-018-0276-y","article-title":"Reference-based analysis of lung single-cell sequencing 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