TY - JOUR
T1 - Spatial dynamic metabolomics identifies metabolic cell fate trajectories in human kidney differentiation
AU - Wang, Gangqi
AU - Heijs, Bram
AU - Kostidis, Sarantos
AU - Rietjens, Rosalie G.J.
AU - Mahfouz, Ahmed
AU - Chuva de Sousa Lopes, Susana M.
AU - van den Berg, Cathelijne W.
AU - van den Berg, Bernard M.
AU - Rabelink, Ton J.
AU - More Authors, null
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - cell metabolism
KW - fetal kidney development
KW - hiPSC-derived kidney organoids
KW - MALDI-MSI
KW - multi-omics metabolomics
KW - nephrogenesis
KW - proximal tubule development
KW - single cell
KW - spatial dynamic metabolomics
UR - http://www.scopus.com/inward/record.url?scp=85141000028&partnerID=8YFLogxK
U2 - 10.1016/j.stem.2022.10.008
DO - 10.1016/j.stem.2022.10.008
M3 - Article
AN - SCOPUS:85141000028
SN - 1934-5909
VL - 29
SP - 1580-1593.e7
JO - Cell Stem Cell
JF - Cell Stem Cell
IS - 11
ER -