title: Metabolome Profiling of Partial and Fully Reprogrammed Induced Pluripotent Stem Cells.
abstract: Acquisition of proper metabolomic fate is required to convert somatic cells toward fully reprogrammed pluripotent stem cells. The majority of induced pluripotent stem cells (iPSCs) are partially reprogrammed and have a transcriptome different from that of the pluripotent stem cells. The metabolomic profile and mitochondrial metabolic functions required to achieve full reprogramming of somatic cells to iPSC status have not yet been elucidated. Clarification of the metabolites underlying reprogramming mechanisms should enable further optimization to enhance the efficiency of obtaining fully reprogrammed iPSCs. In this study, we characterized the metabolites of human fully reprogrammed iPSCs, partially reprogrammed iPSCs, and embryonic stem cells (ESCs). Using capillary electrophoresis time-of-flight mass spectrometry-based metabolomics, we found that 89% of analyzed metabolites were similarly expressed in fully reprogrammed iPSCs and human ESCs (hESCs), whereas partially reprogrammed iPSCs shared only 74% similarly expressed metabolites with hESCs. Metabolomic profiling analysis suggested that converting mitochondrial respiration to glycolytic flux is critical for reprogramming of somatic cells into fully reprogrammed iPSCs. This characterization of metabolic reprogramming in iPSCs may enable the development of new reprogramming parameters for enhancing the generation of fully reprogrammed human iPSCs.
authors.affiliation: 1 Department of Stem Cell Biology, Konkuk University School of Medicine , Seoul, Republic of Korea.
authors.forename: Soon-Jung
authors.initials: SJ
authors.lastname: Park
authors.affiliation: 2 Soonchunhyang Institute of Medi-bio Science (SIMS) and Institute of Tissue Regeneration, Soon Chun Hyang University , Cheonan-si, Chungcheongnam-do, Republic of Korea.
authors.forename: Sang A
authors.initials: SA
authors.lastname: Lee
authors.affiliation: 3 Pediatrics, Indiana University School of Medicine , Indianapolis, Indiana.
authors.forename: Nutan
authors.initials: N
authors.lastname: Prasain
authors.affiliation: 4 Mirae Cell Bio, Inc. , Seoul, Republic of Korea.
authors.forename: Daekyeong
authors.initials: D
authors.lastname: Bae
authors.affiliation: 2 Soonchunhyang Institute of Medi-bio Science (SIMS) and Institute of Tissue Regeneration, Soon Chun Hyang University , Cheonan-si, Chungcheongnam-do, Republic of Korea.
authors.forename: Hyunsu
authors.initials: H
authors.lastname: Kang
authors.affiliation: 2 Soonchunhyang Institute of Medi-bio Science (SIMS) and Institute of Tissue Regeneration, Soon Chun Hyang University , Cheonan-si, Chungcheongnam-do, Republic of Korea.
authors.forename: Taewon
authors.initials: T
authors.lastname: Ha
authors.affiliation: 1 Department of Stem Cell Biology, Konkuk University School of Medicine , Seoul, Republic of Korea.
authors.forename: Jong Soo
authors.initials: JS
authors.lastname: Kim
authors.affiliation: 5 Department of Medicine, Konkuk University School of Medicine , Seoul, Republic of Korea.
authors.forename: Ki-Sung
authors.initials: KS
authors.lastname: Hong
authors.affiliation: 6 Department of Microbiology and Immunology, Indiana University School of Medicine , Indianapolis, Indiana.
authors.forename: Charlie
authors.initials: C
authors.lastname: Mantel
authors.affiliation: 5 Department of Medicine, Konkuk University School of Medicine , Seoul, Republic of Korea.
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Moon
authors.affiliation: 6 Department of Microbiology and Immunology, Indiana University School of Medicine , Indianapolis, Indiana.
authors.forename: Hal E
authors.initials: HE
authors.lastname: Broxmeyer
authors.affiliation: 2 Soonchunhyang Institute of Medi-bio Science (SIMS) and Institute of Tissue Regeneration, Soon Chun Hyang University , Cheonan-si, Chungcheongnam-do, Republic of Korea.
authors.forename: Man Ryul
authors.initials: MR
authors.lastname: Lee
mesh_terms: D002460:Cell Line; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D055442:Metabolome
keywords: metabolism; metabolomics; oxidative phosphorylation; reprogramming efficiency