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 - Koning, Marije
AU - Yuan, Lushun
AU - Tiemeier, Gesa L.
AU - Mahfouz, Ahmed
AU - Dumas, S. bastien J.
AU - Giera, Martin
AU - Kers, Jesper
AU - Chuva de Sousa Lopes, Susana M.
AU - van den Berg, Cathelijne W.
AU - van den Berg, Bernard M.
AU - Rabelink, Ton J.
N1 - Funding Information: The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW) is supported by Novo Nordisk Foundation grants ( NNF21CC0073729 ). G.W. was financially supported by Prof. Jaap de Graeff-Lingling Wiyadharma subsidy of the Leiden University Fund (LUF) and the China Scholarship Council grant. Financial support by Marie Skłodowska-Curie Individual Fellowship to Sebastien J. Dumas is gratefully acknowledged. Financial support by the China Scholarship Council grant to Lushun Yuan is gratefully acknowledged. We thank Ellen Lievers (LUMC, Leiden, the Netherlands) for technical assistance. We thank Christian Freund (hiPSC core facility, LUMC, Leiden, the Netherlands) for providing cell line LUMC0072iCTRL01 and Melissa Little (Murdoch Children’s Research Institute, Melbourne, Australia) for iPSC-MAFB. We are grateful to the staff of the Vrelinghuis, Utrecht, for their efforts in obtaining the human fetal material as well as the donors that have consented for the use of the material. We thank Manon Zuurmond (LUMC, Leiden, the Netherlands) for illustration of graphical abstract. Publisher Copyright: © 2022 The Author(s)
PY - 2022/11/3
Y1 - 2022/11/3
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 - MALDI-MSI
KW - cell metabolism
KW - fetal kidney development
KW - hiPSC-derived kidney organoids
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 - https://doi.org/10.1016/j.stem.2022.10.008
DO - https://doi.org/10.1016/j.stem.2022.10.008
M3 - Article
C2 - 36332571
SN - 1934-5909
VL - 29
SP - 1580-1593.e7
JO - Cell Stem Cell
JF - Cell Stem Cell
IS - 11
ER -