Parallel MultiOMIC Analysis Reveals Glutamine Deprivation Enhances Directed Differentiation of Renal Organoids

Overview

Journal bioRxiv

Date 2025 Mar 10

PMID 40060393

Authors

Iman Sarami

Katherine E Hekman

Ashwani Kumar Gupta

Justin M Snider

David Ivancic

Manja Zec

Manoj Kandpal

Issam Ben-Sahra

Rajasree Menon

Edgar A Otto

Floyd H Chilton

Jason A Wertheim

Affiliations

Soon will be listed here.

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.

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