@article{7a6f2cc965ea4170bf357d09e0af8bc7,
title = "Prdm16 is required for the maintenance of neural stem cells in the postnatal forebrain and their differentiation into ependymal cells",
abstract = "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, Prdm16 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 Prdm16 deletion during fetal development using Nestin-Cre prevented the formation of ependymal cells, disrupting cerebrospinal fluid flow and causing hydrocephalus. Postnatal Prdm16 deletion using Nestin-CreERT2 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.",
keywords = "Ependymal cell, Hydrocephalus, Neural stem cell, Prdm16",
author = "Shimada, {Issei S.} and Melih Acar and Burgess, {Rebecca J.} and Zhiyu Zhao and Morrison, {Sean J.}",
note = "Funding Information: We thank Dr. Bruce Spiegelman for providing Prdm16flox mice, and Dr. Patrick Seale for providing anti-Prdm16 antibody and technical advice for using it for ChIP. We also thank Vishal Khi-vansara, Saikat Mukhopadhyay, Jian Xu, Andrew DeVilbiss, and Woo-Ping Ge for discussing results. We thank BioHPC at University of Texas Southwestern for providing high-performance computing resources, and the Live Cell Imaging Facility (National Institute of Health [NIH] S10RR029731), the Electron Microscopy Core (NIH S10OD020103), the Molecular Pathology Core, and the Quantitative Morphology Core at University of Texas Southwestern Medical Center. S.J.M. is a Howard Hughes Medical Institute Investigator, the Mary McDermott Cook Chair in Pediatric Genetics, the Kathryne and Gene Bishop Distinguished Chair in Pediatric Research, the director of the Hamon Laboratory for Stem Cells and Cancer, and a Cancer Prevention and Research Institute of Texas Scholar. This work was supported by the NIH (R37 AG024945 and R01 NS040750). I.S.S. was supported by a post-doctoral fellowship from the American Heart Association. I.S.S. performed most of the experiments. M.A. and R.J.B. performed some of the experiments in Figures 2, 3, and 6. Z.Z. analyzed the RNA-seq data and performed the statistical analyses. I. S.S. and S.J.M. designed the experiments, interpreted the results, and wrote the manuscript. Publisher Copyright: {\textcopyright} 2017 Shimada et al.",
year = "2017",
doi = "10.1101/gad.291773.116",
language = "English (US)",
volume = "31",
pages = "1134--1146",
journal = "Genes and Development",
issn = "0890-9369",
publisher = "Cold Spring Harbor Laboratory Press",
number = "11",
}