{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:19:42Z","timestamp":1787530782418,"version":"build-2736575974"},"reference-count":41,"publisher":"SAGE Publications","issue":"17-18","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Wayne State University Grant Boost Program and US Department of Defense (DoD) HRRP grant","award":["RH220010"],"award-info":[{"award-number":["RH220010"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Stem Cells and Development"],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:p>\n                    The cochlear nucleus (CN) is the first central relay of auditory information, receiving input from spiral ganglion neurons (SGNs) through specialized synapses whose molecular regulation remains incompletely defined. Here, we examined the role of Progranulin (\n                    <jats:italic toggle=\"yes\">Grn<\/jats:italic>\n                    ) in a stem cell\u2013based CN synaptogenesis using an\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    coculture model. DsRed-expressing mouse embryonic stem cells were differentiated into SGN-like neurons (deSGNs) and cocultured for 4 days with primary CN neurons isolated from postnatal days 3\u20136 wild-type (\n                    <jats:italic toggle=\"yes\">\n                      Grn\n                      <jats:sup>+\/+<\/jats:sup>\n                    <\/jats:italic>\n                    ) or\n                    <jats:italic toggle=\"yes\">Grn<\/jats:italic>\n                    -deficient (\n                    <jats:italic toggle=\"yes\">\n                      Grn\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    ) mice. Cocultures containing\n                    <jats:italic toggle=\"yes\">\n                      Grn\n                      <jats:sup>+\/+<\/jats:sup>\n                    <\/jats:italic>\n                    mouse CN neurons exhibited abundant neurite interactions and synaptic puncta between deSGNs and CN neurons. In contrast, neural connectivity and synaptic puncta were markedly reduced in cocultures with\n                    <jats:italic toggle=\"yes\">\n                      Grn\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mouse CN neurons. Supplementation with recombinant Progranulin protein significantly restored neurite connectivity and synaptic puncta formation in\n                    <jats:italic toggle=\"yes\">\n                      Grn\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mouse CN neuron cocultures. Dose\u2013response analysis further demonstrated that Progranulin concentrations of 0.1\u20131 \u00b5M effectively rescued neurite connection and synaptic features to levels comparable to those observed in\n                    <jats:italic toggle=\"yes\">\n                      Grn\n                      <jats:sup>+\/+<\/jats:sup>\n                    <\/jats:italic>\n                    mouse CN neuron cocultures. These findings identify\n                    <jats:italic toggle=\"yes\">Grn<\/jats:italic>\n                    as a critical regulator of CN synapse formation\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    and provide mechanistic insight relevant to stem cell\u2013based strategies aimed at reconstructing SGN\u2013CN synapses for future auditory repair.\n                  <\/jats:p>","DOI":"10.1177\/15473287261472696","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T09:12:11Z","timestamp":1785489131000},"page":"348-357","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Regulation of Cochlear Nucleus Synaptogenesis by Progranulin in a Stem Cell\u2013Based Coculture Model"],"prefix":"10.1177","volume":"35","author":[{"given":"Anika","family":"Tabassum","sequence":"first","affiliation":[{"name":"Department of Otolaryngology-HNS, Wayne State University School of Medicine, Detroit, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pagadala Praveena","family":"Reddy","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-HNS, Wayne State University School of Medicine, Detroit, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oluwafemi","family":"Agboola","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-HNS, Wayne State University School of Medicine, Detroit, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-HNS, Wayne State University School of Medicine, Detroit, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2975-8635","authenticated-orcid":false,"given":"Zhengqing","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-HNS, Wayne State University School of Medicine, Detroit, Michigan, 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