Metabolic shift in density-dependent stem cell differentiation

Cell Communication and Signaling

Research

Kara E. McCloskey¹  Drew E. Glaser¹  William Turner¹  Fabian V. Filipp²  Simar J. Singh² 

[1] Program for Biological Engineering and Small-scale Technologies, School of Engineering, University of California Merced, 5200 North Lake Road, 95343, Merced, CA, USA;Systems Biology and Cancer Metabolism, Program for Quantitative Systems Biology, University of California Merced, 2500 North Lake Road, 95343, Merced, CA, USA;

关键词: Stem cells;    Differentiation;    Vascular fate;    Cell seeding density;    Systems biology;    Metabolism;    NMR;    Metabolomics;    Fluorescence-activated cell sorting;    Flow cytometry;    Cell adhesion;    Cell contact;    Cell communication;    Microenvironment;    Cancer stem cells;    Embryonic stem cells;    Vascular progenitor cells;    Endothelial cells;   

DOI  :  10.1186/s12964-017-0173-2

 received in 2016-10-26, accepted in 2017-05-02,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundVascular progenitor cells (VPCs) derived from embryonic stem cells (ESCs) are a valuable source for cell- and tissue-based therapeutic strategies. During the optimization of endothelial cell (EC) inductions from mouse ESCs using our staged and chemically-defined induction methods, we found that cell seeding density but not VEGF treatment between 10 ng/mL and 40 ng/mL was a significant variable directing ESCs into FLK1+ VPCs during stage 1 induction. Here, we examine potential contributions from cell-to-cell signaling or cellular metabolism in the production of VPCs from ESCs seeded at different cell densities.MethodsUsing 1D 1H-NMR spectroscopy, transcriptomic arrays, and flow cytometry, we observed that the density-dependent differentiation of ESCs into FLK1+ VPCs positively correlated with a shift in metabolism and cellular growth.ResultsSpecifically, cell differentiation correlated with an earlier plateauing of exhaustive glycolysis, decreased lactate production, lower metabolite consumption, decreased cellular proliferation and an increase in cell size. In contrast, cells seeded at a lower density of 1,000 cells/cm2 exhibited increased rates of glycolysis, lactate secretion, metabolite utilization, and proliferation over the same induction period. Gene expression analysis indicated that high cell seeding density correlated with up-regulation of several genes including cell adhesion molecules of the notch family (NOTCH1 and NOTCH4) and cadherin family (CDH5) related to vascular development.ConclusionsThese results confirm that a distinct metabolic phenotype correlates with cell differentiation of VPCs.

【 授权许可】

CC BY   
© The Author(s). 2017