title: Identification of transcription factors for lineage-specific ESC differentiation.
abstract: A network of transcription factors (TFs) determines cell identity, but identity can be altered by overexpressing a combination of TFs. However, choosing and verifying combinations of TFs for specific cell differentiation have been daunting due to the large number of possible combinations of ∼2,000 TFs. Here, we report the identification of individual TFs for lineage-specific cell differentiation based on the correlation matrix of global gene expression profiles. The overexpression of identified TFs-Myod1, Mef2c, Esx1, Foxa1, Hnf4a, Gata2, Gata3, Myc, Elf5, Irf2, Elf1, Sfpi1, Ets1, Smad7, Nr2f1, Sox11, Dmrt1, Sox9, Foxg1, Sox2, or Ascl1-can direct efficient, specific, and rapid differentiation into myocytes, hepatocytes, blood cells, and neurons. Furthermore, transfection of synthetic mRNAs of TFs generates their appropriate target cells. These results demonstrate both the utility of this approach to identify potent TFs for cell differentiation, and the unanticipated capacity of single TFs directly guides differentiation to specific lineage fates.
authors.affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Kohei
authors.initials: K
authors.lastname: Yamamizu
authors.affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Yulan
authors.initials: Y
authors.lastname: Piao
authors.affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Alexei A
authors.initials: AA
authors.lastname: Sharov
authors.affiliation: Unit on Genetics of Cognition and Behavior, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Veronika
authors.initials: V
authors.lastname: Zsiros
authors.affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.affiliation: Unit on Genetics of Cognition and Behavior, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Kazu
authors.initials: K
authors.lastname: Nakazawa
authors.affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: David
authors.initials: D
authors.lastname: Schlessinger
authors.affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA ; Department of Systems Medicine, Sakaguchi Laboratory, Keio University School of Medicine, Tokyo 160-8582, Japan ; Japan Science and Technology Agency, CREST, Tokyo160-8582, Japan.
authors.forename: Minoru S H
authors.initials: MS
authors.lastname: Ko
mesh_terms: D000818:Animals; D001773:Blood Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D019070:Cell Lineage; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D032342:Muscle Cells / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology
chemical_list: D012333:RNA, Messenger; D014157:Transcription Factors