biostudies-literatureUnknown27(3)Tan JTemasek Life Sciences Laboratory LtdApoE regulates neurogenesis, although how it influences genetic programs remains elusive. Cortical neurons induced from isogenic control and ApoE-/- human neural stem cells (NSCs) recapitulated key transcriptomic signatures of in vivo counterparts identified from single-cell human midbrain. Surprisingly, ApoE expression in NSC and neural progenitor cells (NPCs) is not required for differentiation. Instead, ApoE prevents the over-proliferation of non-neuronal cells during extended neuronal culture when it is not expressed. Elevated miR-199a-5p level in ApoE-/- cells lowers the EZH1 protein and the repressive H3K27me3 mark, a phenotype rescued by miR-199a-5p steric inhibitor. Reduced H3K27me3 at genes linked to extracellular matrix organization and angiogeniScience109231https://www.ebi.ac.uk/biostudies/studies/S-EPMC10909902biostudies-literatureApoE maintains neuronal integrity via microRNA and H3K27me3-mediated repression.PMC10909902Rao VKOng CTTan JNgian ZKZeng XWang JWChong SYTan YYfalseApoE maintains neuronal integrity via microRNA and H3K27me3-mediated repression.ApoE regulates neurogenesis, although how it influences genetic programs remains elusive. Cortical neurons induced from isogenic control and ApoE-/- human neural stem cells (NSCs) recapitulated key transcriptomic signatures of in vivo counterparts identified from single-cell human midbrain. Surprisingly, ApoE expression in NSC and neural progenitor cells (NPCs) is not required for differentiation. Instead, ApoE prevents the over-proliferation of non-neuronal cells during extended neuronal culture when it is not expressed. Elevated miR-199a-5p level in ApoE-/- cells lowers the EZH1 protein and the repressive H3K27me3 mark, a phenotype rescued by miR-199a-5p steric inhibitor. Reduced H3K27me3 at genes linked to extracellular matrix organization and angiogen2024-01-01T00:00:00Z2024 Mar2026-06-16T04:50:03.344Z2025-04-19T22:01:35.661ZS-EPMC109099023843996610.1016/j.isci.2024.109231