Optimal proliferation of a hematopoietic progenitor cell line requires either costimulation with stem cell factor or increase of receptor expression that can be replaced by overexpression of Bcl-2

Huei Mei Huang, Jian Chiuan Li, Yueh Chun Hsieh, Hsin Fang Yang-Yen, Jeffrey Jong Young Yen

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

In vitro proliferation of hematopoietic stem cells requires costimulation by multiple regulatory factors whereas expansion of lineage- committed progenitor cells generated by stem cells usually requires only a single factor. The distinct requirement of factors for proliferation coincides with the differential temporal expression of the subunits of cytokine receptors during early stem cell differentiation. In this study, we explored the underlying mechanism of the requirement of costimulation in a hematopoietic progenitor cell line TF-1. We found that granulocyte-macrophage colony-stimulating factor (GM-CSF) optimally activated proliferation of TF-1 cells regardless of the presence or absence of stem cell factor (SCF). However, interleukin-5 (IL-5) alone sustained survival of TF-1 cells and required costimulation of SCF for optimal proliferation. The synergistic effect of SCF was partly due to its anti-apoptosis activity. Overexpression of the IL-5 receptor α subunit (IL5Rα) in TF-1 cells by genetic selection or retroviral infection also resumed optimal proliferation due to correction of the defect in apoptosis suppression. Exogenous expression of an oncogenic anti-apoptosis protein, Bcl-2, conferred on TF-1 cells an IL-5-dependent phenotype. In summary, our data suggested SCF costimulation is only necessary when the expression level of IL5Rα is low and apoptosis suppression is defective in the signal transduction of IL-5. Expression of BCl-2 proteins released the growth restriction of the progenitor cells and may be implicated in leukemia formation.

Original languageEnglish
Pages (from-to)2569-2577
Number of pages9
JournalBlood
Volume93
Issue number8
Publication statusPublished - Apr 15 1999
Externally publishedYes

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Stem Cell Factor
Hematopoietic Stem Cells
Interleukin-5
Interleukin-5 Receptors
Stem Cells
Stem cells
Cells
Apoptosis
Cell Line
Signal transduction
Cytokine Receptors
Genetic Selection
Granulocyte-Macrophage Colony-Stimulating Factor
Cell Differentiation
Signal Transduction
Leukemia
Proteins
Phenotype
Defects
Growth

ASJC Scopus subject areas

  • Hematology

Cite this

Optimal proliferation of a hematopoietic progenitor cell line requires either costimulation with stem cell factor or increase of receptor expression that can be replaced by overexpression of Bcl-2. / Huang, Huei Mei; Li, Jian Chiuan; Hsieh, Yueh Chun; Yang-Yen, Hsin Fang; Yen, Jeffrey Jong Young.

In: Blood, Vol. 93, No. 8, 15.04.1999, p. 2569-2577.

Research output: Contribution to journalArticle

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