Analyzing Metabolic States of Adipogenic and Osteogenic Differentiation in Human Mesenchymal Stem Cells via Genome Scale Metabolic Model Reconstruction

Autor: Thora Bjorg Sigmarsdottir, Sarah McGarrity, James T. Yurkovich, Óttar Rolfsson, Ólafur Eysteinn Sigurjónsson
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Frontiers in Cell and Developmental Biology, Vol 9 (2021)
Druh dokumentu: article
ISSN: 2296-634X
DOI: 10.3389/fcell.2021.642681
Popis: Since their initial discovery in 1976, mesenchymal stem cells (MSCs) have been gathering interest as a possible tool to further the development and enhancement of various therapeutics within regenerative medicine. However, our current understanding of both metabolic function and existing differences within the varying cell lineages (e.g., cells in either osteogenesis or adipogenesis) is severely lacking making it more difficult to fully realize the therapeutic potential of MSCs. Here, we reconstruct the MSC metabolic network to understand the activity of various metabolic pathways and compare their usage under different conditions and use these models to perform experimental design. We present three new genome-scale metabolic models (GEMs) each representing a different MSC lineage (proliferation, osteogenesis, and adipogenesis) that are biologically feasible and have distinctive cell lineage characteristics that can be used to explore metabolic function and increase our understanding of these phenotypes. We present the most distinctive differences between these lineages when it comes to enriched metabolic subsystems and propose a possible osteogenic enhancer. Taken together, we hope these mechanistic models will aid in the understanding and therapeutic potential of MSCs.
Databáze: Directory of Open Access Journals