The order of expression of transcription factors directs hierarchical specification of hematopoietic lineages

Hiromi Iwasaki, Shin Ichi Mizuno, Yojiro Arinobu, Hidetoshi Ozawa, Yasuo Mori, Hirokazu Shigematsu, Kiyoshi Takatsu, Daniel G. Tenen, Koichi Akashi

Research output: Contribution to journalArticlepeer-review

217 Citations (Scopus)

Abstract

The mechanism of lineage specification in multipotent stem cells has not been fully understood. We recently isolated progenitors with the eosinophil, basophil, or mast cell lineage potential, all of which originate from granulocyte/monocyte progenitors (GMPs). By using these prospectively purified progenitors, we show here that the expression timing of GATA-2 and CCAAT enhancer-binding protein α (C/EBPα) can differentially control their lineage commitment. The expression of GATA-2 instructed C/EBPα-expressing GMPs to commit exclusively into the eosinophil lineage, while it induced basophil and/or mast cell lineage commitment if C/EBPα was suppressed at the GMP stage. Furthermore, simply by switching the order of C/EBPα and GATA-2 transduction, even lymphoid-committed progenitors recaptured these developmental processes to be reprogrammed into each of these lineages. We propose that the order of expression of key transcription factors is critical for their interplay to selectively drive lineage specification programs, by which stem cells could generate multiple lineage cells in a hierarchical manner.

Original languageEnglish
Pages (from-to)3010-3021
Number of pages12
JournalGenes and Development
Volume20
Issue number21
DOIs
Publication statusPublished - Nov 1 2006

All Science Journal Classification (ASJC) codes

  • Genetics
  • Developmental Biology

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