Abstract
BackgroundAdipose-derived mesenchymal stem cells (ADSCs) have been extensively explored as a promising therapeutic agent due to their differentiation, proliferation and migration abilities. The epigenetic mechanisms that regulate the fate of mesenchymal stem cells (MSCs) have been described in detail. However, the epigenetic modulation of ADSCs proliferation and migration is poorly understood.MethodsThe present study examined histone demethylases roles and expression by RT-PCR, as well as through siRNA screening and ChIP-qPCR assay. Cellular proliferation and migration assays were employed in shRNA-mediated JMJD6 knockdown and control ADSCs. PDE1C inhibition studies were conducted to confirm its role in JMJD6-mediated epigenetic regulation of ADSCs.ResultsThe data demonstrate that the histone demethylase JMJD6 plays a critical role in regulating the proliferation and migration of ADSCs by removing H4R3me2a at the promoter regions of PDEC1 and suppressing PDEC1 expression. Importantly, the depletion of JMJD6 in ADSCs significantly increased cellular proliferation and motility, which was associated with increases in PDE1C expression and decreases in the levels of both cAMP and cGMP. The increase in proliferation and migration was reversed by treatment with a PDE1C inhibitor, suggesting that JMJD6 attenuates the proliferation and migration of ADSCs as an epigenetic regulator and PDE1C partially contributes to the JMJD6-mediated regulation.ConclusionsTaken together, our results indicate for the first time that JMJD6 plays an important role in the regulation of ADSCs proliferation and migration through the modulation of PDE1C expression.
Highlights
Adipose-derived mesenchymal stem cells (ADSCs) have been extensively explored as a promising therapeutic agent due to their differentiation, proliferation and migration abilities
Jumonji C domain-containing protein 6 (JMJD6) is critical for cell migration To investigate the potential roles of histone demethylases in the regulation of adipose-derived mesenchymal stem cells (ADSCs) migration, we first profiled the expression of 27 histone demethylases in ADSCs
Consistent with our results from the small interfering RNA (siRNA)-mediated JMJD6 knockdown, ADSCs with JMJD6 depletion resulted in a striking increase in wound-healing ability as compared to cells transfected with the control short hairpin RNAs (shRNA) (Fig. 2c)
Summary
Adipose-derived mesenchymal stem cells (ADSCs) have been extensively explored as a promising therapeutic agent due to their differentiation, proliferation and migration abilities. The epigenetic modulation of ADSCs proliferation and migration is poorly understood. Mesenchymal stem cells (MSCs) can be isolated from a variety of tissues and used for cell-based therapies [1, 2]. The unique adipose-derived mesenchymal stem cells (ADSCs) exhibit similar properties to bone marrow mesenchymal stem cells (BM-MSCs) including proliferative potential and broad differentiation plasticity. ADSCs have been used in several stem cells therapy approaches. A lack of specific accumulation of ADSCs in injured tissues and limited cell proliferation in repeated subcultures in vitro reduces their therapeutic efficacy [3]. ADSCs capacity for differentiation, proliferation, and migration is critical to their efficacy in clinical applications. It has been suggested that MSCs can increase their proliferation rate and migratory activity during certain pathological conditions caused by changes in their microenvironment during tissue repair [4, 5]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
