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

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 RTPCR, 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.