荷兰莱顿大学医学中心Ton J. Rabelink团队近期取得重要工作进展，他们通过研究空间动态代谢组学确定了人类肾脏分化中的代谢细胞命运轨迹。相关论文2022年11月3日在线发表于《细胞—干细胞》杂志上。

研究人员利用多组学平台研究复杂组织中细胞类型特异性代谢动力学，他们发现了发育中人类肾脏发生过程中的代谢轨迹。利用同位素标记的原位分析，在从肾小泡向S形体和近端小管分化的过程中，观察到从糖酵解向脂肪酸β-氧化的转变。研究人员还发现，hiPSC来源的肾类器官以代谢不成熟表型为特征，不能利用线粒体长链脂肪酸进行能量代谢。

此外，补充丁酸盐可促进培养的肾类器官小管上皮分化和成熟。他们的发现强调了理解代谢轨迹与有效引导干细胞分化的相关性。

据介绍，越来越多的证据表明代谢在决定细胞命运中起着重要作用。然而，在承认其组织微环境中的异质性和细胞动力学的空间分辨率下评估代谢是一个挑战。

附：英文原文

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

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

Issue&Volume: 2022/11/03

Abstract: 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.

DOI: 10.1016/j.stem.2022.10.008

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(22)00426-X