Details

Autor(en) / Beteiligte

• Wang, Gangqi
• Heijs, Bram
• Kostidis, Sarantos
• Rietjens, Rosalie G.J.
• Koning, Marije
• Yuan, Lushun
• Tiemeier, Gesa L.
• Mahfouz, Ahmed
• Dumas, Sébastien J.
• Giera, Martin
• Kers, Jesper
• Chuva de Sousa Lopes, Susana M.
• van den Berg, Cathelijne W.
• van den Berg, Bernard M.
• Rabelink, Ton J.

Titel

Spatial dynamic metabolomics identifies metabolic cell fate trajectories in human kidney differentiation

Ist Teil von

• Cell stem cell, 2022-11, Vol.29 (11), p.1580-1593.e7

Ort / Verlag

Elsevier Inc

Erscheinungsjahr

2022

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• Accumulating evidence demonstrates important roles for metabolism in cell fate determination. However, it is a challenge to assess metabolism at a spatial resolution that acknowledges both heterogeneity and cellular dynamics in its tissue microenvironment. Using a multi-omics platform to study cell-type-specific dynamics in metabolism in complex tissues, we describe the metabolic trajectories during nephrogenesis in the developing human kidney. Exploiting in situ analysis of isotopic labeling, a shift from glycolysis toward fatty acid β-oxidation was observed during the differentiation from the renal vesicle toward the S-shaped body and the proximal tubules. In addition, we show that hiPSC-derived kidney organoids are characterized by a metabolic immature phenotype that fails to use mitochondrial long-chain fatty acids for energy metabolism. Furthermore, supplementation of butyrate enhances tubular epithelial differentiation and maturation in cultured kidney organoids. Our findings highlight the relevance of understanding metabolic trajectories to efficiently guide stem cell differentiation. [Display omitted] •Kidney epithelium development follows metabolic trajectories•Proximal tubular development shows a shift from glycolysis to fatty acid β-oxidation•Kidney organoids show a metabolic immature phenotype in the absence of CPT1a expression•Butyrate enhances proximal tubular maturation in kidney organoids In this study, Wang et al. report metabolic trajectories during human kidney epithelium development using spatial dynamic metabolomics. This knowledge can be used to enhance proximal tubule differentiation and maturation in hiPSC-derived kidney organoids.