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https://hdl.handle.net/2440/127262
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Type: | Journal article |
Title: | HOPX regulates bone marrow-derived mesenchymal stromal cell fate determination via suppression of adipogenic gene pathways |
Author: | Hng, C.H. Camp, E. Anderson, P. Breen, J. Zannettino, A. Gronthos, S. |
Citation: | Scientific Reports, 2020; 10(1):1-14 |
Publisher: | Nature Publishing Group |
Issue Date: | 2020 |
ISSN: | 2045-2322 2045-2322 |
Statement of Responsibility: | Chee Ho Hng, Esther Camp, Peter Anderson, James Breen, Andrew Zannettino and Stan Gronthos |
Abstract: | Previous studies of global binding patterns identified the epigenetic factor, EZH2, as a regulator of the homeodomain-only protein homeobox (HOPX) gene expression during bone marrow stromal cell (BMSC) differentiation, suggesting a potential role for HOPX in regulating BMSC lineage specification. In the present study, we confirmed that EZH2 direct binds to the HOPX promoter region, during normal growth and osteogenic differentiation but not under adipogenic inductive conditions. HOPX gene knockdown and overexpression studies demonstrated that HOPX is a promoter of BMSC proliferation and an inhibitor of adipogenesis. However, functional studies failed to observe any affect by HOPX on BMSC osteogenic differentiation. RNA-seq analysis of HOPX overexpressing BMSC during adipogenesis, found HOPX function to be acting through suppression of adipogenic pathways associated genes such as ADIPOQ, FABP4, PLIN1 and PLIN4. These findings suggest that HOPX gene target pathways are critical factors in the regulation of fat metabolism. |
Keywords: | Cells, Cultured Mesenchymal Stem Cells Humans Homeodomain Proteins Tumor Suppressor Proteins Cell Differentiation Cell Proliferation Osteogenesis Adolescent Adult Female Male Adipogenesis Young Adult Enhancer of Zeste Homolog 2 Protein |
Description: | Published: 09 July 2020 |
Rights: | © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
DOI: | 10.1038/s41598-020-68261-2 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1120989 http://purl.org/au-research/grants/nhmrc/1142954 http://purl.org/au-research/grants/nhmrc/1120989 http://purl.org/au-research/grants/nhmrc/1142954 http://purl.org/au-research/grants/nhmrc/1120989 http://purl.org/au-research/grants/nhmrc/1142954 http://purl.org/au-research/grants/nhmrc/1120989 http://purl.org/au-research/grants/nhmrc/1142954 |
Published version: | http://dx.doi.org/10.1038/s41598-020-68261-2 |
Appears in Collections: | Aurora harvest 8 Medicine publications |
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