Identification of transcription factors for lineage-specific ESC differentiation

Kohei Yamamizu, Yulan Piao, Alexei A. Sharov, Veronika Zsiros, Hong Yu, Kazu Nakazawa, David Schlessinger, Minoru S.H. Ko

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39 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)545-559
Number of pages15
JournalStem cell reports
Volume1
Issue number6
DOIs
Publication statusPublished - 2013 Dec 17

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ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

Cite this

Yamamizu, K., Piao, Y., Sharov, A. A., Zsiros, V., Yu, H., Nakazawa, K., Schlessinger, D., & Ko, M. S. H. (2013). Identification of transcription factors for lineage-specific ESC differentiation. Stem cell reports, 1(6), 545-559. https://doi.org/10.1016/j.stemcr.2013.10.006