Abstract
Given their totipotency, human embryonic stem cells (hESCs) can differentiate into all types of cells, including adipocytes, and provide an excellent research model for studying diseases associated with the metabolism of adipocytes, such as obesity and diabetes mellitus. Epigenetic regulation, including DNA methylation and histone modification, plays an essential role in the development and differentiation of hESCs. Lysine-specific demethylase 1 (LSD1), a well-characterized histone-modifying enzyme, demethylates dimethylated histone H3 lysine 4 (H3K4) through a flavin adenine dinucleotide (FAD)-dependent oxidative reaction. LSD1 affects the growth and differentiation of human and mouse ES cells, and the deletion of this gene in mice leads to embryonic lethality. Here, we investigated the functional role of LSD1 during the adipogenic differentiation of hESCs involving the demethylation of H3K4. We also found that treating hESCs with the LSD1 inhibitor CBB1007 promotes the adipogenic differentiation of hESCs.
Highlights
In 1998, human embryonic stem cells were first isolated by Thomson et al [1] and have become a potential source for cell replacement therapies because of their abilities to self-renew and maintain pluripotency with the potential to differentiate into all types of cells
We found that peroxisome proliferatoractivated receptor γ-2 (PPARγ-2) and C/EBPα were expressed in differentiated cells but not in undifferentiated cells, demonstrating that adipogenic differentiation from human embryonic stem cells (hESCs) was successful
This study is the first to study the role of Lysine-specific demethylase 1 (LSD1) in the induction of adipogenic differentiation in hESCs
Summary
In 1998, human embryonic stem cells (hESCs) were first isolated by Thomson et al [1] and have become a potential source for cell replacement therapies because of their abilities to self-renew and maintain pluripotency with the potential to differentiate into all types of cells. The epigenetic modification of chromosomes plays an important role in ES cell maintenance and differentiation [2]. An important aspect of epigenetic regulation is posttranslational histone tail modification, including acetylation, methylation, citrullination, phosphorylation, ubiquitylation, sumoylation, and biotinylation [3]. Among these modifications, methylation marks are dynamically regulated by histone methyltransferases and demethylases [4]. Several studies have reported the role of the dynamic regulation of histone tail methylation in the maintenance of pluripotency in stem cells to block cell differentiation [5, 6]. Histone demethylases have been reported to be associated with a broad spectrum of developmental functions in gametogenesis, embryogenesis and differentiation [7, 8]
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