Parallel multiOMIC analysis reveals glutamine deprivation enhances directed differentiation of renal organoids
Year: 2025
Type: preprint
Abstract: 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.
Institutions: Northwestern University, The University of Texas MD Anderson Cancer Center, Jesse Brown VA Medical Center, Emory University, Atlanta VA Health Care System, University of Arizona, Southern Arizona VA Health Care System, University of Colorado Anschutz, Rockefeller University Hospital, Northwestern Medicine, University of Michigan
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: The USC (Re)Building the Kidney Coordinating Center, University of Michigan O'Brien Kidney Translational Core Center, Modulating senescence in induced pluripotent stem cell-derived endothelial cells for vascular disease modeling and therapy, Repairing the Kidney Endothelium via Targeted Extracellular Matrix Modifiers, The Robert H. Lurie Comprehensive Cancer Center, Developing, Demonstrating, and Disseminating Innovative Programs to Achieve Translational Success
OpenAlex ID: W4408083467