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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Apr 26, 2015; 7(3): 583-595
Published online Apr 26, 2015. doi: 10.4252/wjsc.v7.i3.583
Role of Hox genes in stem cell differentiation
Anne Seifert, David F Werheid, Silvana M Knapp, Edda Tobiasch
Anne Seifert, David F Werheid, Silvana M Knapp, Edda Tobiasch, Department of Applied Sciences, Bonn-Rhine-Sieg University of Applied Sciences, 53359 Rheinbach, Germany
Author contributions: Seifert A, Werheid DF, Knapp SM and Tobiasch E contributed to this paper.
Supported by BMBF, AdiPaD, 1720X06, BMBF, FHprofUnt, FKZ: 03FH012PB2; FH-Extra, “Europäischer Fonds für regionale Entwicklung”, “Europa-Investition in unsere Zukunft”, FKZ: z1112fh012; EFRE co-financed NRW Ziel 2: “Regionale Wettbewerbsfähigkeit und Beschäftigung”, DAAD, PPP Vigoni, FKZ: 314-vigoni-dr and FKZ: 54669218 for Edda Tobiasch.
Conflict-of-interest: The authors certify that there is no conflict of interest with any organization or entity with financial interests or non-financial interests, including commercial, personal, political, intellectual, or religious interests, regarding the material discussed in the manuscript.
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: Edda Tobiasch, Professor, Department of Applied Sciences, Bonn-Rhine-Sieg University of Applied Sciences, von-Liebig-Str. 20, 53359 Rheinbach, Germany. edda.tobiasch@h-brs.de
Telephone: +49-2241-865576 Fax: +49-2241-8658576
Received: July 29, 2014
Peer-review started: July 29, 2014
First decision: October 16, 2014
Revised: December 1, 2014
Accepted: December 16, 2014
Article in press: December 17, 2014
Published online: April 26, 2015
Processing time: 268 Days and 6.2 Hours
Abstract

Hox genes are an evolutionary highly conserved gene family. They determine the anterior-posterior body axis in bilateral organisms and influence the developmental fate of cells. Embryonic stem cells are usually devoid of any Hox gene expression, but these transcription factors are activated in varying spatial and temporal patterns defining the development of various body regions. In the adult body, Hox genes are among others responsible for driving the differentiation of tissue stem cells towards their respective lineages in order to repair and maintain the correct function of tissues and organs. Due to their involvement in the embryonic and adult body, they have been suggested to be useable for improving stem cell differentiations in vitro and in vivo. In many studies Hox genes have been found as driving factors in stem cell differentiation towards adipogenesis, in lineages involved in bone and joint formation, mainly chondrogenesis and osteogenesis, in cardiovascular lineages including endothelial and smooth muscle cell differentiations, and in neurogenesis. As life expectancy is rising, the demand for tissue reconstruction continues to increase. Stem cells have become an increasingly popular choice for creating therapies in regenerative medicine due to their self-renewal and differentiation potential. Especially mesenchymal stem cells are used more and more frequently due to their easy handling and accessibility, combined with a low tumorgenicity and little ethical concerns. This review therefore intends to summarize to date known correlations between natural Hox gene expression patterns in body tissues and during the differentiation of various stem cells towards their respective lineages with a major focus on mesenchymal stem cell differentiations. This overview shall help to understand the complex interactions of Hox genes and differentiation processes all over the body as well as in vitro for further improvement of stem cell treatments in future regenerative medicine approaches.

Keywords: Genes; Homeobox; Stem cells; Asymmetric cell division; Mesenchymal stromal cells; Growth; Development; Regeneration; Patterning; Cell lineage

Core tip:Hox genes are involved in embryonic development as well as in repair mechanisms in the adult body, thus regulating cell fate. These genes have also been found to be driving factors in various stem cell differentiations in vitro and in vivo which makes them interesting tools for future improvements in stem cell therapies. Therefore, this review outlines the involvement of Hox genes in various stem cell differentiations with a major emphasis on mesenchymal stem cell differentiations.