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Transcriptome analysis of Stem Cells from Human Umbilical Cord Blood

ABSTRACT: Uncovering the molecular mechanism of stem cell self-renewal is critical to broaden current therapeutic applications and to understand how its de-regulation may lead to pathological conditions. In this work, we report changes in gene expression and related cell processes during conditions of high in vitro expansion of CD133+/CD34+ primitive stem cells from human umbilical cord blood (UCB). Based on DNA microarray assays, we demonstrate that primary metabolism and cell cycle genes are specifically up-regulated, as well as members of the Wnt and Notch signaling pathways. Estradiol (E2) treatment resulted in enhanced cell expansion, which was correlated with activation of MEK/ERK signaling genes and inhibition of GLI2, a member of the Hedgehog pathway. Most notably, E2-induced CD133+/CD34+ cell expansion was highly associated to regulation of genes disrupted in cancer, such as the recently described DOCK4 and SPARCL1 tumor suppressor genes. Quantitative real-time PCR analysis confirmed down-regulation of DOCK4 and SPARCL1 in E2-treated CD133+/CD34+ cells and parallel results were verified when comparing their expression in mononuclear blood cells of chronic myeloid leukemia patients and healthy individuals. The striking differential expression of cancer-associated genes found reveals potential molecular targets for oncogenic transformation of CD133+/CD34+ cells and strengthens the importance of pre-clinical studies assessing safety of stem cell expansion protocols for therapeutic application. Keywords: dose response

ORGANISM(S): Homo sapiens

PROVIDER: GSE4609 | GEO | 2007/04/05

SECONDARY ACCESSION(S): PRJNA94399

REPOSITORIES: GEO

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Transcriptome analysis of Stem Cells from Human Umbilical Cord Blood

Project description:Uncovering the molecular mechanism of stem cell self-renewal is critical to broaden current therapeutic applications and to understand how its de-regulation may lead to pathological conditions. In this work, we report changes in gene expression and related cell processes during conditions of high in vitro expansion of CD133+/CD34+ primitive stem cells from human umbilical cord blood (UCB). Based on DNA microarray assays, we demonstrate that primary metabolism and cell cycle genes are specifically up-regulated, as well as members of the Wnt and Notch signaling pathways. Estradiol (E2) treatment resulted in enhanced cell expansion, which was correlated with activation of MEK/ERK signaling genes and inhibition of GLI2, a member of the Hedgehog pathway. Most notably, E2-induced CD133+/CD34+ cell expansion was highly associated to regulation of genes disrupted in cancer, such as the recently described DOCK4 and SPARCL1 tumor suppressor genes. Quantitative real-time PCR analysis confirmed down-regulation of DOCK4 and SPARCL1 in E2-treated CD133+/CD34+ cells and parallel results were verified when comparing their expression in mononuclear blood cells of chronic myeloid leukemia patients and healthy individuals. The striking differential expression of cancer-associated genes found reveals potential molecular targets for oncogenic transformation of CD133+/CD34+ cells and strengthens the importance of pre-clinical studies assessing safety of stem cell expansion protocols for therapeutic application. Keywords: dose response Gene expression intensities were measured using CodeLink Human Whole Genome Bioarrays.

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