Identification of Transcription Factors for Lineage-Specific ESC Differentiation

Stem Cell Reports. 2013 Nov 27;1(6):545-59. doi: 10.1016/j.stemcr.2013.10.006. eCollection 2013.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Cells / cytology
  • Blood Cells / metabolism
  • Cell Differentiation / genetics*
  • Cell Line
  • Cell Lineage
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Hepatocytes / cytology
  • Hepatocytes / metabolism
  • Mice
  • Muscle Cells / cytology
  • Muscle Cells / metabolism
  • Neurons / cytology
  • Neurons / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription Factors / physiology

Substances

  • RNA, Messenger
  • Transcription Factors