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Pregnant exposure of Valproic acid (VPA) is an important environmental risk factor for ASD, but it's long\u2010term effects on the development of human neural cells, particularly in vivo, and the corresponding treatment have yet been fully investigated. In the present study, we first made a humanized ASD mouse model by transplanting VPA\u2010pretreated human neural progenitor cells (hNPCs) into the cortex of immune\u2010deficient mice. In comparison with wild type and control chimeric mice, ASD chimeric mice (<jats:sup>VPA<\/jats:sup>hNPC mice) exhibit core syndromes of ASD, namely dramatic reduction of sociability, social interaction and social communication, and remarkable increase of stereotype repetitive behaviors and anxiety\u2010like behaviors. At cellular level, VPA\u2010pretreatment biased the differentiation of human excitatory neurons and their axonal projections in host brain. Chemogenetic suppression of human neuronal activity restored most behavior abnormalities of <jats:sup>VPA<\/jats:sup>hNPC mice. Further, specific modulation of human neurons by a newly developed transcranial magnetic stimulation (TMS) device which could precisely target hPNCs effectively recued the core syndromes of ASD\u2010like behaviors, restored the excitatory\u2010inhibitory neuronal differentiation and axonal projection, and reversed the expression of over half of the VPA\u2010affected genes. These data demonstrated that <jats:sup>VPA<\/jats:sup>hNPC mice could be used as a humanized model of ASD and that precisely targeted TMS could ameliorate the VPA\u2010biased human neuronal differentiation in vivo.<\/jats:p>","DOI":"10.1002\/btm2.10748","type":"journal-article","created":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T01:51:12Z","timestamp":1737683472000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Amelioration of biased neuronal differentiation in humanized mouse model of valproic acid\u2010induced autism by precisely targeted transcranial magnetic stimulation"],"prefix":"10.1002","volume":"10","author":[{"given":"Yilin","family":"Hou","sequence":"first","affiliation":[{"name":"Department of Military Medical Psychology Air Force Medical University  Xi'an Shaanxi P. R. 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