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Lysophosphatidic acid Shifts Metabolic and Transcriptional Landscapes to Induce a Novel Cellular State in Human Embryonic Stem Cells

ABSTRACT: Pluripotent stem cells can be maintained in a continuum of cellular states with distinct features. Exogenous lipid supplements are commonly utilized to shift the balance of global metabolism relieving the dependence on de novo lipogenesis. However, it is largely unexplored how specific lipid components regulate metabolism and pluripotency state. In this study, we investigate the impact of lipid supplements on human embryonic stem cells (hESCs), and report that signaling lipid lysophosphatidic acid (LPA) is the key component to shift the metabolic landscape in lipid supplement AlbuMAX. Although the maintenance of ERK phosphorylation and primed pluripotency is independent of exogenous lipids, LPA increases ERK phosphorylation, especially upon niche disintegration. We further demonstrate that LPA leads to distinctive transcriptome profile that is not associated with de novo lipogenesis. We also show that LPA causes unique and reversible phenotypes in cell cycle, morphology and mitochondria. This study reveals an LPA -induced primed state that allow people to drastically alter cell physiology for basic research and stem cell applications with hESCs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE198007 | GEO | 2022/03/08

REPOSITORIES: GEO

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Transcriptional impacts of lipids on hESC

Project description:Pluripotent stem cells can be maintained in a continuum of cellular states with distinct features. Exogenous lipid supplements are commonly utilized to shift the balance of global metabolism relieving the dependence on de novo lipogenesis. However, it is largely unexplored how specific lipid components regulate metabolism and pluripotency state. In this study, we investigate the impact of lipid supplements on human embryonic stem cells (hESCs), and report that signaling lipid lysophosphatidic acid (LPA) is the key component to shift the metabolic landscape in lipid supplement AlbuMAX. Although the maintenance of ERK phosphorylation and primed pluripotency is independent of exogenous lipids, LPA increases ERK phosphorylation, especially upon niche disintegration. We further demonstrate that LPA leads to distinctive transcriptome profile that is not associated with de novo lipogenesis. We also show that LPA causes unique and reversible phenotypes in cell cycle, morphology and mitochondria. This study reveals an LPA -induced primed state that allow people to drastically alter cell physiology for basic research and stem cell applications with hESCs.

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2024-02-12 | MTBLS7832 | MetaboLights

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Project description:Human embryonic stem cells (hESCs) can self-renew infinitely, or differentiate into the three germ layer lineages in vitro with certain cues, holding great promise to model early human embryo development ex vivo.It is wildly accepted that hESCs take advantage of both glycolysis and mitochondrial respiration to favor the naïve pluripotency, while prefer glycolysis to support the primed pluripotency. Thus, the function of mitochondrial respiration in primed hESCs has been underestimated for a long time, and has not been fully understood yet. Herein, we report that the adenosine triphosphate (ATP) production rate is comparable between mitochondrial respiration and glycolysis, suggesting that mitoATP serves as one of the major sources of the ATP pool in primed hESCs. Next, we constructed a OGDH knockdown cell line whose ability of mitochondrial respiration was impired. Of note, OGDH deficiency led to the exit of primed pluripotency accompanied by cell death.Collectively, the current study unveils that OGDH acts as a key regulator to fine-tune the abundance of TCA cycle metabolites to ensure the mitochondrial respiration activity in primed hESCs, and highlights the pivotal roles of mitochondrial respiration in terms of ATP production and the maintenance of primed pluripotency.

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