Differential gene expression underlying the functional distinctions of primary human CD34+ hematopoietic stem and progenitor cells from peripheral blood and bone marrow

Ulrich Steidl, Ralf Kronenwett, Rainer Haas

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

The restorative capacity of human CD34+ hematopoietic cells is clinically used in the autologous and allogeneic transplant setting to support cytotoxic therapy. We examined gene expression patterns of highly enriched bone marrow CD34+ (BM-CD34+) or G-CSF-mobilized peripheral blood CD34+ (PB-CD34+) cells by cDNA array technology, quantitative real-time RT-PCR, and flow cytometry, to identify molecular causes underlying the functional differences between circulating and sedentary hematopoietic stem and progenitor cells. The greater cell cycle and DNA synthesis activity of BM-CD34+ compared to PB-CD34+ cells was reflected by the 2- to 5-fold higher expression of 9 genes involved in cell cycle, 11 genes regulating DNA synthesis, and the cell cycle-initiating transcription factor E2F-1. The 2- to 3-fold greater expression of 5 pro-apoptotic genes in PB-CD34+ cells indicated a higher apoptotic activity, which could functionally be corroborated by apoptosis assays. Thrombin receptor (PAR1 ), known to play a role in trafficking of malignant cells, was 3.6-fold higher expressed in circulating CD34+ cells than in BM-CD34+ cells. Guidance via thrombin receptor might molecularly mediate stem cell migration. In summary, our study provides gene expression profiles of primary human CD34+ hematopoietic cells of blood and marrow. Our data molecularly confirm and explain the finding that CD34+ cells residing in the bone marrow are cycling more rapidly, whereas circulating CD34+ cells consist of a higher number of quiescent stem and progenitor cells. Moreover, our data give novel molecular insights into stem cell migration and differentiation.

Original languageEnglish (US)
Pages (from-to)89-100
Number of pages12
JournalAnnals of the New York Academy of Sciences
Volume996
DOIs
StatePublished - Jan 1 2003
Externally publishedYes

Keywords

  • Cell cycle
  • DNA replication
  • Gene expression profiling
  • Genetics
  • Hematopoietic stem cells
  • Migration
  • Transcription factors

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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