Genome-wide expression profiling and functional network analysis upon neuroectodermal conversion of human mesenchymal stem cells suggest HIF-1 and miR-124a as important regulators.
Exp Cell Res
; 316(17): 2760-78, 2010 Oct 15.
Article
em En
| MEDLINE
| ID: mdl-20599952
ABSTRACT
Tissue-specific stem cells, such as bone-marrow-derived human mesenchymal stem cells (hMSCs), are thought to be lineage restricted and therefore, could only be differentiated into cell types of the tissue of origin. Several recent studies however have suggested that these types of stem cells might be able to break barriers of germ layer commitment and differentiate in vitro into cells with neuroectodermal properties. We reported earlier about efficient conversion of adult hMSCs into a neural stem cell (NSC)-like population (hmNSCs, for human marrow-derived NSC-like cells) with all major properties of NSCs including functional neuronal differentiation capacity. Here we compared the transcriptomes from hMSCs and hmNSCs using a novel strategy by combining classic Affymetrix oligonucleotide microarray profiling with regulatory and protein interaction network analyses to shed light on regulatory protein networks involved in this neuroectodermal conversion process. We found differential regulation of extracellular matrix protein transcripts, up-regulation of distinct neuroectodermal and NSCs marker genes and local chromosomal transcriptional up-regulation at chromosome 4q13.3. In comparison to hMSCs and primary adult hippocampal NSCs, the transcriptome of hmNSCs displayed minor overlap with both other cell populations. Advanced bioinformatics of regulated genes upon neuroectodermal conversion identified transcription factor networks with HIF-1 and microRNA miR-124a as potential major regulators. Together, transgerminal neuroectodermal conversion of hMSCs into NSC-like cells is accompanied by extensive changes of their global gene expression profile, which might be controlled in part by transcription factor networks related to HIF-1 and miR-124a.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Genoma Humano
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Perfilação da Expressão Gênica
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MicroRNAs
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Fator 1 Induzível por Hipóxia
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Redes Reguladoras de Genes
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Placa Neural
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Células-Tronco Mesenquimais
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
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Adult
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Humans
Idioma:
En
Revista:
Exp Cell Res
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Alemanha