Shimada Issei S, Acar Melih, Burgess Rebecca J, Zhao Zhiyu, Morrison Sean J
Children's Research Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Genes Dev. 2017 Jun 1;31(11):1134-1146. doi: 10.1101/gad.291773.116. Epub 2017 Jul 11.
We and others showed previously that PR domain-containing 16 (Prdm16) is a transcriptional regulator required for stem cell function in multiple fetal and neonatal tissues, including the nervous system. However, germline knockout mice died neonatally, preventing us from testing whether Prdm16 is also required for adult stem cell function. Here we demonstrate that Prdm16 is required for neural stem cell maintenance and neurogenesis in the adult lateral ventricle subventricular zone and dentate gyrus. We also discovered that Prdm16 is required for the formation of ciliated ependymal cells in the lateral ventricle. Conditional deletion during fetal development using Nestin-Cre prevented the formation of ependymal cells, disrupting cerebrospinal fluid flow and causing hydrocephalus. Postnatal deletion using -CreER did not cause hydrocephalus or prevent the formation of ciliated ependymal cells but caused defects in their differentiation. Prdm16 was required in neural stem/progenitor cells for the expression of Foxj1, a transcription factor that promotes ependymal cell differentiation. These studies show that Prdm16 is required for adult neural stem cell maintenance and neurogenesis as well as the formation of ependymal cells.
我们及其他研究人员之前表明，含PR结构域16（Prdm16）是多种胎儿及新生儿组织（包括神经系统）中干细胞功能所需的转录调节因子。然而，种系敲除小鼠在出生时死亡，这使我们无法测试Prdm16对成体干细胞功能是否也是必需的。在此，我们证明Prdm16是成体侧脑室室下区和齿状回中神经干细胞维持及神经发生所必需的。我们还发现Prdm16是侧脑室中纤毛室管膜细胞形成所必需的。利用Nestin-Cre在胎儿发育期间进行条件性缺失可阻止室管膜细胞的形成，扰乱脑脊液流动并导致脑积水。使用-CreER在出生后进行缺失不会导致脑积水或阻止纤毛室管膜细胞的形成，但会导致其分化缺陷。Prdm16在神经干/祖细胞中是促进室管膜细胞分化的转录因子Foxj1表达所必需的。这些研究表明，Prdm16是成体神经干细胞维持、神经发生以及室管膜细胞形成所必需的。
