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Published on: July 25, 2016
KDM4C Contributes to Trophoblast-like Stem Cell Conversion from Porcine-Induced Pluripotent Stem Cells (piPSCs) via
Shuai Yu1,2, Qiaoyan Shen1, Rui Zhang1
1College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, No. 22 Xinong Road, Yangling District, Xianyang 712100, China.
Insights
Epigenetic modifications in porcine stem cells reveal KDM4C
Area of Science:
- Epigenetics and Stem Cell Biology
- Mammalian Embryo Development
- Chromatin Regulation
Background:
- Understanding epigenetic regulation in porcine-induced pluripotent stem cells (piPSCs) converting to trophoblast-like stem cells (TLSCs) is crucial for early embryo development.
- The epigenetic modification network governing this conversion remains largely unexplored.
Purpose of the Study:
- To investigate global changes in histone modifications during piPSC to TLSC conversion.
- To elucidate the role of KDM4C in regulating pluripotency and cell fate during this transition.
Main Methods:
- Global analysis of histone H3 Lysine 4, 9, 27, 36 methylation and Lysine 27 acetylation in piPSCs and TLSCs.
- Investigating the function of KDM4C via inhibitor studies and gene replenishment experiments.
- Assessing pluripotency markers (AP staining) and cell proliferation.
Main Results:
- TLSCs exhibit a distinct H3K36me2 modification profile compared to piPSCs.
- KDM4C, a H3K36me3/2 demethylase, is upregulated in TLSCs and regulates pluripotency.
- KDM4C overexpression represses proliferation and promotes trophoblast differentiation markers (CDX2, KRT8).
Conclusions:
- KDM4C plays a critical role in determining piPSC fate during conversion to TLSCs, potentially replacing ESRRB function.
- KDM4C-mediated epigenetic modifications are key to understanding piPSC to TSC lineage determination.
Abstract:
Studies on ESRRB-regulating porcine-induced pluripotent stem cells (piPSCs) converted to trophoblast-like stem cells (TLSCs) contribute to the understanding of early embryo development. However, the epigenetic modification regulation network during the conversion is poorly understood. Here, the global change in histone H3 Lysine 4, 9, 27, 36 methylation and Lysine 27 acetylation was investigated in piPSCs and TLSCs. We found a high modification profile of H3K36me2 in TLSCs compared to that of piPSCs, whereas the profiles of other modifications remained constant. KDM4C, a H3K36me3/2 demethylase, whose gene body region was combined with ESRRB, was upregulated in TLSCs. Moreover, KDM4 inhibitor supplementation rescued the AP-negative phenotype observed in TLSCs, confirming that KDM4C could regulate the pluripotency of TLSCs. Subsequently, KDM4C replenishment results show the significantly repressed proliferation and AP-positive staining of TLSCs. The expressions of CDX2 and KRT8 were also upregulated after KDM4C overexpression. In summary, these results show that KDM4C replaced the function of ESRRB. These findings reveal the unique and crucial role of KDM4C-mediated epigenetic chromatin modifications in determination of piPSCs' fate and expand the understanding of the connection between piPSCs and TSCs.
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