{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:27:54Z","timestamp":1768505274382,"version":"3.49.0"},"posted":{"date-parts":[[2023,1,13]]},"group-title":"Neuroscience","reference-count":61,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,1,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Cochlear hair cell loss is a leading cause of deafness in humans. Neighboring supporting cells have some capacity to regenerate hair cells. However, their regenerative potential sharply declines as supporting cells undergo maturation (postnatal day 5 in mice). We recently reported that reactivation of the RNA-binding protein LIN28B restores the hair cell-regenerative potential of P5 cochlear supporting cells. Here, we identify the LIN28B target\n                  <jats:italic>Trim71<\/jats:italic>\n                  as a novel and equally potent enhancer of supporting cell plasticity. TRIM71 is a critical regulator of stem cell behavior and cell reprogramming, however, its role in cell regeneration is poorly understood. Employing an organoid-based assay, we show that TRIM71 reactivation increases the mitotic and hair cell-forming potential of P5 cochlear supporting cells by facilitating their de-differentiation into progenitor-like cells. Our mechanistic work indicates that TRIM71\u2019s RNA-binding activity is essential for such ability, and our transcriptomic analysis identifies gene modules that are linked to TRIM71 and LIN28B-mediated supporting cell reprogramming. Furthermore, our study uncovers that the TRIM71-LIN28B target\n                  <jats:italic>Hmga2<\/jats:italic>\n                  is essential for supporting cell self-renewal and hair cell formation.\n                <\/jats:p>","DOI":"10.1101\/2023.01.12.523802","type":"posted-content","created":{"date-parts":[[2023,1,13]],"date-time":"2023-01-13T19:40:16Z","timestamp":1673638816000},"source":"Crossref","is-referenced-by-count":0,"title":["Reactivation of the progenitor gene Trim71 enhances the mitotic and hair cell-forming potential of cochlear supporting cells"],"prefix":"10.64898","author":[{"given":"Xiao-Jun","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles","family":"Morgan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prathamesh T","family":"Nadar-Ponniah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Waldemar","family":"Kolanus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7424-2112","authenticated-orcid":false,"given":"Angelika","family":"Doetzlhofer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023011707300832000_2023.01.12.523802v1.1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.114926"},{"key":"2023011707300832000_2023.01.12.523802v1.2","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.devcel.2022.03.001","article-title":"Single-cell transcriptome analysis reveals three sequential phases of gene expression during zebrafish sensory hair cell regeneration","volume":"57","year":"2022","journal-title":"Dev Cell"},{"key":"2023011707300832000_2023.01.12.523802v1.3","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5421.1837"},{"key":"2023011707300832000_2023.01.12.523802v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3519"},{"key":"2023011707300832000_2023.01.12.523802v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2009.02.028"},{"key":"2023011707300832000_2023.01.12.523802v1.6","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1202774109"},{"key":"2023011707300832000_2023.01.12.523802v1.7","doi-asserted-by":"publisher","DOI":"10.1101\/gad.187641.112"},{"key":"2023011707300832000_2023.01.12.523802v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2017.09.015"},{"key":"2023011707300832000_2023.01.12.523802v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109016"},{"key":"2023011707300832000_2023.01.12.523802v1.10","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2783"},{"key":"2023011707300832000_2023.01.12.523802v1.11","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/s41593-022-01043-3","article-title":"Impaired neurogenesis alters brain biomechanics in a neuroprogenitor-based genetic subtype of congenital hydrocephalus","volume":"25","year":"2022","journal-title":"Nat Neurosci"},{"key":"2023011707300832000_2023.01.12.523802v1.12","doi-asserted-by":"crossref","unstructured":"Evsen, L. , Li, X. , Zhang, S. , Razin, S. & Doetzlhofer, A. 2020. let-7 miRNAs inhibit CHD7 expression and control auditory-sensory progenitor cell behavior in the developing inner ear. 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