Review
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Mar 26, 2015; 7(2): 300-314
Published online Mar 26, 2015. doi: 10.4252/wjsc.v7.i2.300
Imprinted Zac1 in neural stem cells
Guillaume Daniel, Udo Schmidt-Edelkraut, Dietmar Spengler, Anke Hoffmann
Guillaume Daniel, Udo Schmidt-Edelkraut, Dietmar Spengler, Anke Hoffmann, Max Planck Institute of Psychiatry, Translational Research, 80804 Munich, Germany
Author contributions: Daniel G, Schmidt-Edelkraut U, Spengler D and Hoffmann A jointly contributed to this paper.
Supported by Max Planck Institute of Psychiatry.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dietmar Spengler, MD, Max Planck Institute of Psychiatry, Translational Research, Kraepelinstrasse 2-10, 80804 Munich, Germany. spengler@mpipsykl.mpg.de
Telephone: +49-89-30622587 Fax: +49-89-30622605
Received: July 25, 2014
Peer-review started: July 25, 2014
First decision: August 28, 2014
Revised: September 24, 2014
Accepted: November 17, 2014
Article in press: November 19, 2014
Published online: March 26, 2015
Abstract

Neural stem cells (NSCs) and imprinted genes play an important role in brain development. On historical grounds, these two determinants have been largely studied independently of each other. Recent evidence suggests, however, that NSCs can reset select genomic imprints to prevent precocious depletion of the stem cell reservoir. Moreover, imprinted genes like the transcriptional regulator Zac1 can fine tune neuronal vs astroglial differentiation of NSCs. Zac1 binds in a sequence-specific manner to pro-neuronal and imprinted genes to confer transcriptional regulation and furthermore coregulates members of the p53-family in NSCs. At the genome scale, Zac1 is a central hub of an imprinted gene network comprising genes with an important role for NSC quiescence, proliferation and differentiation. Overall, transcriptional, epigenomic, and genomic mechanisms seem to coordinate the functional relationships of NSCs and imprinted genes from development to maturation, and possibly aging.

Keywords: Zac1, Cell fate decisions, Neural stem cells, Genomic imprinting, Igf2-H19, Dlk1, p57Kip2, Necdin, Differentiation, Imprinted gene networks

Core tip: Both neural stem cells (NSCs) and imprinted genes participate in the same developmental processes. Here, we will explore the possibility that these two processes actually interact with each other. We will exemplarily consider the role of single imprinted genes in NSC biology based on their functional relationship to the imprinted gene Zac1, which is itself at the focus of this review due to its role in directing neuronal vs astroglial differentiation of NSCs and as a central hub of an imprinted gene network comprising genes important to NSC biology.