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Glutamine deprivation enhances directed differentiation of renal organoids

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE128939 | GEO | 2022/06/01

REPOSITORIES: GEO

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Parallel multiOMIC analysis reveals glutamine deprivation enhances directed differentiation of renal organoids.

Project description:Metabolic pathways play a critical role in driving differentiation but remain poorly understood in the development of kidney organoids. In this study, parallel metabolite and transcriptome profiling of differentiating human pluripotent stem cells (hPSCs) to multicellular renal organoids revealed key metabolic drivers of the differentiation process. In the early stage, transitioning from hPSCs to nephron progenitor cells (NPCs), both the glutamine and the alanine-aspartate-glutamate pathways changed significantly, as detected by enrichment and pathway impact analyses. Intriguingly, hPSCs maintained their ability to generate NPCs, even when deprived of both glutamine and glutamate. Surprisingly, single cell RNA-Seq analysis detected enhanced maturation and enrichment for podocytes under glutamine-deprived conditions. Together, these findings illustrate a novel role of glutamine metabolism in regulating podocyte development.

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Glutamine deprivation enhances directed differentiation of renal organoids

Project description:Glutamine deprivation enhances directed differentiation of renal organoids

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Glutamine deprivation enhances metabolic reprogramming during kidney organoid directed differentiation

Project description:In this study, we systematically performed comprehensive metabolite and transcriptome profiling of human pluripotent stem cells (hPSCs) during differentiation into NPCs and later into multicellular organoids. We found activation of distinct metabolic pathways during early stage progression from hPSCs to NPCs; however, NPCs, organoids, and the intervening developmental stages between them shared similar metabolic profiles across this later stage of maturation. Importantly, the Alanine-aspartate-glutamate and glutamine pathways were significantly altered during the first stages of differentiation. Moreover, hPSCs survived glutamine deprivation during in vitro differentiation, and NPCs were successfully generated both in the absence and presence of glutamine and glutamate. Surprisingly, metabolic deprivation resulted in enhanced maturation, specifically in podocytes, as evidenced through single cell RNA-Seq analysis. These findings highlight the critical regulatory role of glutamine metabolism in the derivation of nephron progenitor cells and kidney organoids.

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