{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:36:54Z","timestamp":1785411414945,"version":"3.56.0"},"reference-count":56,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Beijing Hospitals Authority\u2019s Ascent Plan","award":["DFL20240804"],"award-info":[{"award-number":["DFL20240804"]}]},{"award":["DFL20240804"],"award-info":[{"award-number":["DFL20240804"]}],"id":[{"id":"https:\/\/ror.org\/02jwb5s28","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Hui Zhi talent project","award":["HZ2021ZCLJ004"],"award-info":[{"award-number":["HZ2021ZCLJ004"]}]},{"award":["HZ2021ZCLJ004"],"award-info":[{"award-number":["HZ2021ZCLJ004"]}],"id":[{"id":"https:\/\/ror.org\/015bdn754","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171250"],"award-info":[{"award-number":["82171250"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82171250"],"award-info":[{"award-number":["82171250"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005088","name":"Beijing Municipal Health Commission Fund","doi-asserted-by":"publisher","award":["PXM2020_026283_000005"],"award-info":[{"award-number":["PXM2020_026283_000005"]}],"id":[{"id":"10.13039\/501100005088","id-type":"DOI","asserted-by":"publisher"}]},{"award":["PXM2020_026283_000005"],"award-info":[{"award-number":["PXM2020_026283_000005"]}],"id":[{"id":"https:\/\/ror.org\/0374a5s68","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Project for Technology Development of Beijing-affiliated Medical Research Institutes","award":["11000023T000002036310"],"award-info":[{"award-number":["11000023T000002036310"]}]},{"award":["11000023T000002036310"],"award-info":[{"award-number":["11000023T000002036310"]}],"id":[{"id":"https:\/\/ror.org\/045n75910","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Current protocols for generating cortical interneurons from human pluripotent stem cells are hindered by slow differentiation kinetics and poor reproducibility across cell lines. Here, we present a defined small-molecule-based strategy that efficiently directs human-induced neural stem cells (hiNSCs) toward cortical GABAergic interneurons within 14\u201318 days, which is substantially faster than conventional methods. Short-term dual-SMAD and WNT inhibition rapidly commits hiNSCs to an interneuron progenitor fate, reaching transcriptional states equivalent to those obtained with prolonged protocols. Prolonged activation of Sonic Hedgehog (via SAG) further enhances lineage specification, markedly upregulating NKX2.1, FOXG1, GABA, somatostatin (SST), and parvalbumin (PV) expression, and enriching pathways associated with early functional maturation. Importantly, RNA-sequencing reveals that under identical induction conditions, hiNSCs differentiate more rapidly and homogeneously than human-induced pluripotent stem cells (hiPSCs), which exhibit broader, less lineage-focused transcriptional trajectories. This differentiation strategy is highly reproducible across four genetically distinct hiNSC lines, with minimal off-target populations. Functionally, hiNSC-derived cortical interneurons display robust migratory behavior, produce abundant GABA, and survive transplantation into the adult mouse hippocampus, where they extend processes and form synapse-like structures. These findings establish a rapid, scalable, and robust approach for generating human cortical interneurons, supporting their safety and integration potential as a foundation for future cell replacement strategies in neurological disorders.<\/jats:p>","DOI":"10.3390\/ijms27125194","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:43:54Z","timestamp":1780965834000},"page":"5194","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Rapid and Robust Generation of Human Cortical Interneurons from Induced Neural Stem Cells"],"prefix":"10.3390","volume":"27","author":[{"given":"Xinwei","family":"Zang","sequence":"first","affiliation":[{"name":"Cell Therapy Center, Beijing Municipal Geriatric Medical Research Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, China"},{"name":"National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Beijing 100053, China"},{"name":"Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Xuanwu Hospital, Capital Medical University, Beijing 100053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunqian","family":"Guan","sequence":"additional","affiliation":[{"name":"Cell Therapy Center, Beijing Municipal Geriatric Medical Research Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, China"},{"name":"National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Beijing 100053, China"},{"name":"Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Xuanwu Hospital, Capital Medical University, Beijing 100053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanting","family":"Xing","sequence":"additional","affiliation":[{"name":"Cell Therapy Center, Beijing Municipal Geriatric Medical Research Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, China"},{"name":"National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Beijing 100053, China"},{"name":"Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Xuanwu Hospital, Capital Medical University, Beijing 100053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1508-510X","authenticated-orcid":false,"given":"Zhiguo","family":"Chen","sequence":"additional","affiliation":[{"name":"Cell Therapy Center, Beijing Municipal Geriatric Medical Research Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, China"},{"name":"National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Beijing 100053, China"},{"name":"Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Xuanwu Hospital, Capital Medical University, Beijing 100053, China"},{"name":"Center of Parkinson\u2019s Disease, Beijing Institute for Brain Disorders, Beijing 100069, China"},{"name":"Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing 100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s13287-023-03302-x","article-title":"A beginner\u2019s guide on the use of brain organoids for neuroscientists: A systematic review","volume":"14","author":"Mulder","year":"2023","journal-title":"Stem Cell Res. 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