title: E2F1 Orchestrates Transcriptomics and Oxidative Metabolism in Wharton's Jelly-Derived Mesenchymal Stem Cells from Growth-Restricted Infants.
abstract: Wharton's jelly-derived Mesenchymal Stem Cells (MSCs) isolated from newborns with intrauterine fetal growth restriction were previously shown to exert anabolic features including insulin hypersensitivity. Here, we extend these observations and demonstrate that MSCs from small for gestational age (SGA) individuals have decreased mitochondrial oxygen consumption rates. Comparing normally grown and SGA MSCs using next generation sequencing studies, we measured global transcriptomic and epigenetic profiles and identified E2F1 as an over-expressed transcription factor regulating oxidative metabolism in the SGA group. We further show that E2F1 regulates the differential transcriptome found in SGA derived MSCs and is associated with the activating histone marks H3K27ac and H3K4me3. One of the key genes regulated by E2F1 was found to be the fatty acid elongase ELOVL2, a gene involved in the endogenous synthesis of docosahexaenoic acid (DHA). Finally, we shed light on how the E2F1-ELOVL2 pathway may alter oxidative respiration in the SGA condition by contributing to the maintenance of cellular metabolic homeostasis.
authors.affiliation: Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore, Singapore.
authors.forename: Peck Yean
authors.initials: PY
authors.lastname: Tan
authors.affiliation: Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore, Singapore.
authors.forename: Cheng Wei
authors.initials: CW
authors.lastname: Chang
authors.affiliation: Singapore Immunology Network, Agency for Science Technology and Research (A*STAR), Singapore, Singapore.
authors.forename: Kaibo
authors.initials: K
authors.lastname: Duan
authors.affiliation: Singapore Immunology Network, Agency for Science Technology and Research (A*STAR), Singapore, Singapore.
authors.forename: Michael
authors.initials: M
authors.lastname: Poidinger
authors.affiliation: Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Kai Lyn
authors.initials: KL
authors.lastname: Ng
authors.affiliation: Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore, Singapore.|Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Yap Seng
authors.initials: YS
authors.lastname: Chong
authors.affiliation: Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore, Singapore.|Liggins Institute, University of Auckland, Auckland, New Zealand.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Gluckman
authors.affiliation: Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore, Singapore.
authors.forename: Walter
authors.initials: W
authors.lastname: Stünkel
mesh_terms: D050687:E2F1 Transcription Factor / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D010641:Phenotype; D059467:Transcriptome; D015854:Up-Regulation; D059631:Wharton Jelly / Q000378:metabolism*
chemical_list: D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D006657:Histones