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

Hartmut Beug, Richard Dahl, Peter Steinlein, Susanne Meyer, Eva Maria Deiner, Michael J. Hayman

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 cells of either the erythroid or myeloid lineages. These committed 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)58-72
Number of pages15
JournalOncogene
Volume11
Issue number1
StatePublished - Jul 6 1995
Externally publishedYes

Fingerprint

Oncogene Proteins
Intercellular Signaling Peptides and Proteins
Erythroid Cells
Stem Cells
Growth Differentiation Factors
Apoptosis
Receptor Protein-Tyrosine Kinases
Myeloid Cells
Genetic Therapy
Growth Hormone
Cell Biology
Leukemia
Transcription Factors
Steroids
Hormones
Ligands
In Vitro Techniques
Growth
Proteins

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

Cite this

Beug, H., Dahl, R., Steinlein, P., Meyer, S., Deiner, E. M., & Hayman, M. J. (1995). In vitro growth of factor-dependent multipotential hematopoietic cells is induced by the nuclear oncoprotein v-Ski. Oncogene, 11(1), 58-72.

In vitro growth of factor-dependent multipotential hematopoietic cells is induced by the nuclear oncoprotein v-Ski. / Beug, Hartmut; Dahl, Richard; Steinlein, Peter; Meyer, Susanne; Deiner, Eva Maria; Hayman, Michael J.

In: Oncogene, Vol. 11, No. 1, 06.07.1995, p. 58-72.

Research output: Contribution to journalArticle

Beug, H, Dahl, R, Steinlein, P, Meyer, S, Deiner, EM & Hayman, MJ 1995, 'In vitro growth of factor-dependent multipotential hematopoietic cells is induced by the nuclear oncoprotein v-Ski', Oncogene, vol. 11, no. 1, pp. 58-72.
Beug, Hartmut ; Dahl, Richard ; Steinlein, Peter ; Meyer, Susanne ; Deiner, Eva Maria ; Hayman, Michael J. / In vitro growth of factor-dependent multipotential hematopoietic cells is induced by the nuclear oncoprotein v-Ski. In: Oncogene. 1995 ; Vol. 11, No. 1. pp. 58-72.
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