Neurogenesis contributes to poststroke recovery. Long noncoding RNAs (lncRNAs) participate in the regulation of stem cell self‐renewal and differentiation. However, the role of lncRNAs in stroke‐induced neurogenesis remains unknown. In this study, we found that H19 was the most highly upregulated lncRNA in neural stem cells (NSCs) of the subventricular zone (SVZ) of rats subjected to focal cerebral ischemia. Deletion of H19 suppressed cell proliferation, promoted cell death, and blocked NSC differentiation. RNA sequencing analysis revealed that genes deregulated by H19 knockdown were those that are involved in transcription, apoptosis, proliferation, cell cycle, and response to hypoxia. H19 knockdown significantly increased the transcription of cell cycle‐related genes including p27, whereas overexpression of H19 substantially reduced expression of these genes through the interaction with chromatin remodeling proteins EZH2 and SUZ12. Moreover, H19 regulated neurogenesis‐related miRNAs. Inactivation of H19 in NSCs of ischemic rats attenuated spontaneous functional recovery after stroke. Collectively, our data provide novel insights into the epigenetic regulation of lncRNAs in stroke‐induced neurogenesis.

中文翻译：

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长链非编码 RNA 介导中风诱导的神经发生

神经发生有助于卒中后恢复。长链非编码 RNA (lncRNA) 参与干细胞自我更新和分化的调控。然而，lncRNAs 在中风诱导的神经发生中的作用仍然未知。在本研究中，我们发现 H19 是局灶性脑缺血大鼠脑室下区 (SVZ) 神经干细胞 (NSC) 中上调程度最高的 lncRNA。H19 的删除抑制细胞增殖，促进细胞死亡，并阻止 NSC 分化。RNA 测序分析显示，被 H19 敲低解除调节的基因是那些参与转录、凋亡、增殖、细胞周期和对缺氧反应的基因。H19 敲低显着增加了细胞周期相关基因的转录，包括 p27、而 H19 的过表达通过与染色质重塑蛋白 EZH2 和 SUZ12 的相互作用显着降低了这些基因的表达。此外，H19 调节神经发生相关的 miRNA。缺血大鼠神经干细胞中 H19 的失活减弱了中风后的自发功能恢复。总的来说，我们的数据为 lncRNA 在中风诱导的神经发生中的表观遗传调控提供了新的见解。