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Recently, <jats:italic>APOE<\/jats:italic> has been shown to play an important role in the regulation of HN. However, the time\u2010dependent impact of its polymorphism in humans remains elusive, partially due to the difficulties of studying human HN in vivo. To bridge this gap of knowledge, we used an in vitro cellular model of human HN and performed a time course characterization on isogenic induced pluripotent stem cells with different genotypes of <jats:italic>APOE<\/jats:italic>. We found that <jats:italic>APOE<\/jats:italic> itself was more highly expressed in \u03b54 at the stem cell stage, while the divergence of differential gene expression phenotype between \u03b54 and \u03b53 became prominent at the neuronal stage of differentiation. This divergence was not associated with the differential capacity to generate dentate gyrus granule cell\u2010like neurons, as its level was comparable between \u03b54 and \u03b53. Transcriptomic profiling across different stages of neurogenesis indicated a clear \u201cmaturation of functional neurons\u201d phenotype in \u03b53 neural progenitors and neurons, while genes differentially expressed only in \u03b54 neurons suggested potential alterations in \u201cmetabolism and mitochondrial function.\u201d Taken together, our in vitro investigation suggests that <jats:italic>APOE<\/jats:italic> \u03b54 allele can exert a transcriptome\u2010wide effect at the later stages of HN, without altering the overall level of neurogenesis per se.<\/jats:p>","DOI":"10.1002\/hipo.23502","type":"journal-article","created":{"date-parts":[[2023,1,29]],"date-time":"2023-01-29T06:44:16Z","timestamp":1674974656000},"page":"322-346","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["In vitro characterization on the role of <scp><i>APOE<\/i><\/scp> polymorphism in human hippocampal neurogenesis"],"prefix":"10.1002","volume":"33","author":[{"given":"Hyunah","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience King's College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jack","family":"Price","sequence":"additional","affiliation":[{"name":"Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience King's College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deepak P.","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience King's College London  London UK"},{"name":"MRC Centre for Neurodevelopmental Disorders King's College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1260-8083","authenticated-orcid":false,"given":"Sandrine","family":"Thuret","sequence":"additional","affiliation":[{"name":"Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience King's College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,1,28]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2010-11-10-r106"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.08.004"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2014.10.003"},{"key":"e_1_2_9_5_1","unstructured":"Blighe K. 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