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Regeneration of neural cells in irradiation\u2010induced cerebellar injury has been reported, but the underlying mechanism remains elusive.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We established an irradiation\u2010induced developing cerebellum injury model in neonatal mice. Microarray, KEGG analysis and semi in vivo slice culture were performed for mechanistic study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Nestin\u2010expressing progenitors (NEPs) but not granule neuron precursors (GNPs) were resistant to irradiation and able to regenerate after irradiation. NEPs underwent less apoptosis but similar DNA damage following irradiation compared with GNPs. Subsequently, they started to proliferate and contributed to granule neurons regeneration dependent on the sonic hedgehog (Shh) pathway. In addition, irradiation increased Shh ligand provided by Purkinje cells. And microglia accumulated in the irradiated cerebellum producing more IFN\u2010\u03b3, which augmented Shh ligand production to promote NEP proliferation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>NEP was radioresistant and regenerative. IFN\u2010\u03b3 was increased post irradiation to upregulate Shh ligand, contributing to NEP regeneration. Our study provides insight into the mechanisms of neural cell regeneration in irradiation injury of the developing cerebellum and will help to develop new therapeutic targets for minimizing the side effects of radiotherapy for brain tumors.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.14485","type":"journal-article","created":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T09:12:48Z","timestamp":1696410768000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["IFN\u2010\u03b3 promotes radioresistant Nestin\u2010expressing progenitor regeneration in the developing cerebellum by augmenting Shh ligand production"],"prefix":"10.1111","volume":"30","author":[{"given":"Jian","family":"Hu","sequence":"first","affiliation":[{"name":"Pediatric Cancer Center, Jiangsu Key Laboratory of Neuropsychiatric Diseases, Department of Pharmacology, College of Pharmaceutical Sciences Soochow University  Suzhou 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