Elevation of Survivin levels by hematopoietic growth factors occurs in quiescent CD34+ hematopoietic stem and progenitor cells before cell cycle entry.

Seiji Fukuda, Louis Pelus

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Survivin is a member of the inhibitor of apoptosis protein (IAP) family that is overexpressed during G(2)/M phase in most cancer cells. In contrast, we previously reported that Survivin is expressed throughout the cell cycle in normal CD34(+) hematopoietic stem and progenitor cells stimulated by the combination of Thrombopoietin (Tpo), Stem Cell Factor (SCF) and Flt3 ligand (FL). In order to address whether Survivin expression is specifically up-regulated by hematopoietic growth factors before cell cycle entry, we isolated quiescent CD34(+) cells and investigated Survivin expression in response to growth factor stimulation. Survivin is up-regulated in CD34(+) cells with 2N DNA content following growth factor addition, suggesting it becomes elevated during G(0)/G(1). Survivin is barely detectable in freshly isolated umbilical cord blood (UCB) Ki-67(negative) and Cyclin D(negative) CD34(+) cells, however incubation with Tpo, SCF and FL for 20 hrs results in up-regulation without entry of cells into cell cycle. Culture of G(0) CD34(+) cells isolated based on Hoechst 33342/PyroninY staining with Tpo, SCF and FL for 48 hrs, results in significantly elevated Survivin mRNA and protein levels. Moreover, labeling of fresh G(0) CD34(+) cells with 5-(and 6-) carboxyfluorescein diacetate succinimidyl ester (CFSE) before culture with growth factors for up to 72 hrs, revealed that Survivin expression was elevated in CFSE(bright) G(0) CD34(+) cells, indicating that up-regulation occurred before entry into G1. These results suggest that up-regulation of Survivin expression in CD34(+) cells is an early event in cell cycle entry that is regulated by hematopoietic growth factors and does not simply reflect cell cycle progression and cell division.

Original languageEnglish
Pages (from-to)322-326
Number of pages5
JournalCell Cycle
Volume1
Issue number5
StatePublished - Sep 2002

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Hematopoietic Stem Cells
Intercellular Signaling Peptides and Proteins
Cell Cycle
Cells
Thrombopoietin
Stem Cell Factor
Hematopoietic Cell Growth Factors
Up-Regulation
Inhibitor of Apoptosis Proteins
Cyclin D
Cell Division
Cell culture
Labeling
Blood
Fetal Blood
Messenger RNA
DNA
Staining and Labeling
flt3 ligand protein
Proteins

ASJC Scopus subject areas

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Cite this

Elevation of Survivin levels by hematopoietic growth factors occurs in quiescent CD34+ hematopoietic stem and progenitor cells before cell cycle entry. / Fukuda, Seiji; Pelus, Louis.

In: Cell Cycle, Vol. 1, No. 5, 09.2002, p. 322-326.

Research output: Contribution to journalArticle

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