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| Status |
Public on Apr 05, 2007 |
| Title |
Transcriptome analysis of Stem Cells from Human Umbilical Cord Blood |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
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
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| |
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| Overall design |
Gene expression intensities were measured using CodeLink Human Whole Genome Bioarrays.
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| |
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| Contributor(s) |
Okamoto OK, Vêncio RZ |
| Citation(s) |
17559657 |
| Submission date |
Apr 05, 2006 |
| Last update date |
Oct 28, 2014 |
| Contact name |
Ricardo Z.N. Vêncio |
| Organization name |
Universidade de São Paulo
|
| Department |
Computing and Mathematics Department
|
| Lab |
http://labpib.fmrp.usp.br
|
| Street address |
Av. Bandeirantes, 3900
|
| City |
Ribeirao Preto |
| State/province |
SP |
| ZIP/Postal code |
14049-900 |
| Country |
Brazil |
| |
|
| Platforms (2) |
| GPL2891 |
GE Healthcare/Amersham Biosciences CodeLink™ UniSet Human 20K I Bioarray |
| GPL2895 |
GE Healthcare/Amersham Biosciences CodeLink Human Whole Genome Bioarray |
|
| Samples (3) |
| GSM100833 |
Umbilical cord blood cells transcriptome - T00234774 |
| GSM100940 |
Umbilical cord blood cells cultivated 7 days and 1h - T00239851 |
| GSM103110 |
Umbilical cord blood cells cultivated 7 days then 1h-treatment with Estradiol - T00239853 |
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| Relations |
| BioProject |
PRJNA94399 |
