In vitro growth of factor-dependent multipotential hematopoietic cells is induced by the nuclear oncoprotein v-Ski

H. Beug, R. Dahl, P. Steinlein, S. Meyer, E. M. Deiner, M. J. Hayman

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Understanding how self renewal, commitment and differentiation are regulated in normal, multipotent hematopoietic progenitors is important for our understanding of underlying mechanisms involved in leukemogenesis. In addition, knowledge of progenitor cell biology is critical if these cells are to be used for gene therapy. In this communication, we demonstrate that the oncogenic transcription factor v-Ski, together with the ligand activated receptor tyrosine kinase c-Kit, induces the continuous in vitro self renewal of primary avian multipotent progenitors. These cells have an in vitro life span of > 100 generations. In addition they spontaneously differentiate into cells of the erythroid, monocytic and granulocytic lineages. If clonal strains of these multipotent progenitors are exposed to specific mixtures of growth factors and hormones, they develop into committed the erythroid or myeloid lineages, cells underwent efficient terminal differentiation when they were treated with the relevant lineage-specific growth/differentiation factors, but underwent apoptosis when exposed to the incorrect factors for the respective lineage. While the committed cells coexpress marker proteins from different lineages, expression of the 'wrong' lineage marker is repressed during terminal differentiation. Our results indicate that a combination of v-Ski and activated c-Kit induces long-term self renewal in primary multipotent progenitors, which can be induced to commit and differentiate along specific lineages under different, defined conditions. Our data also suggest that growth factors and steroid hormones control terminal differentiation by a combined induction of commitment, growth and apoptosis, a process likely to be affected in stem cell leukemias.

Original languageEnglish (US)
Pages (from-to)59-72
Number of pages14
JournalOncogene
Volume11
Issue number1
StatePublished - Jan 1 1995
Externally publishedYes

Keywords

  • Cytokines
  • Hematopoiesis
  • Multipotent progenitors
  • Ski
  • Steroid hormones
  • c-Kit

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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