Transcriptional Profiling Reflects Shared and Unique Characters for CD34⁺and CD133⁺Cells

Abstract

CD34 and CD133 are the most commonly used markers to enrich hematopoietic stem cells (HSCs). Positively selected HSCs are increasingly used for autologous and allogeneic transplantation, yet the biological properties of CD34(+) and CD133(+) cells are largely unknown. In the present study, a genome-wide gene expression analysis of human cord blood (CB)-derived CD34(+) cells was performed. The CD34(+) gene expression profile was compared to an identically constructed CD133(+) gene expression profile to reveal the specific expression patterns and major differences of CD34(+) and CD133(+) cells. As expected, many genes were similarly expressed in the two cell populations, but cell-type-specific gene expression was also demonstrated. Self-organizing map analysis was used to identify transcripts having similar expression patterns, and the results were compared between CD34(+) and CD133(+) cells. Also, a prioritization algorithm was used to rank the genes best separating CD34(+) and CD133(+) cells from their CD34() and CD133() counterparts in CB. Our results show that CD133(+) cells have higher numbers of up-regulated genes than CD34(+) cells. Furthermore, the uniquely expressed genes in CD34(+) or CD133(+) cell populations were associated with different biological processes. CD34(+) cells overexpressed many transcripts associated with development and response to stress or external stimuli. In CD133(+) cells, the most significantly represented biological processes were establishment and maintenance of chromatin architecture, DNA metabolism, and cell cycle. The differences between the gene expression profiles of CD34(+) and CD133(+) cells indicate the more primitive nature of CD133(+) cells. These profiles suggest that CD34(+) and CD133(+) cells may have different roles in hematopoietic regeneration.

LDOC1 mRNA is differentially expressed in chronic lymphocytic leukemia and predicts overall survival in untreated patients

“…A recent study that evaluated the gene expression profiles of human cord blood subpopulations identified LDOC1 mRNA as up-regulated in the CD34 ϩ /CD133 ϩ subpopulation, which contains hematopoietic stem cells and progenitor cells, compared with the more mature CD34 Ϫ /CD133 Ϫ subpopulation. 25 Taken together, these findings suggest that during the course of normal B-cell development LDOC1 mRNA levels may vary with maturational stage and state of activation. An assessment of B cells obtained from different compartments and subjected to a variety of different stimuli is required to address this question.…”

Isolation and Enrichment of Stem Cells

“…Thus, CD133 + cells in the hematopoietic system appear to be ancestral to CD34 + cells, especially as the latter can be generated in vitro from CD133 + CD34 − cells [66] . Furthermore, CD133 + cells from cord blood display a higher proliferative activity [66,67] and a more primitive gene expression profile [68] than CD34 + cells. Thus far, the phenotype of CD34-negative HSCs has been characterized by the concurrent absence of CD38, lack of lineage-specific cell surface antigens, as well as by expression of CD133 [69] .…”

Flow Cytometric Immunophenotyping of Umbilical Cord and Peripheral Blood Haematopoietic Progenitor Cells by Different CD34 Epitopes, CD133, P-Glycoprotein Expression and Rhodamine-123 Efflux

“…A comparative determination of the reactivity to mAb against CD133 and the ability to exclude Rho123 was performed to see whether these markers correlate with specific CD34 epitope patterns or with each other. By using transcriptional profiling analysis [35], (global) gene expression [36][37][38] and functional analysis [16,39,40], many authors have reported that CD133+ cells reflect a more primitive stage of HPC. This was characterised by a high content of scid-re-populating and long-term culture-initiating cells [15].…”