Silencing BRE expression in human umbilical cord perivascular (HUCPV) progenitor cells accelerates osteogenic and chondrogenic differentiation

Autor: Mei Kuen Tang, Yiu-Loon Chui, Lok Man Lo, Winifred Wing Yiu Yau, Kenneth Ka Ho Lee, Elve Chen, Xuesong Yang, John Yeuk-Hon Chan, Yao Yao
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Proteomics
Proteome
Tumor Physiology
Cellular differentiation
Gene Expression
lcsh:Medicine
Epigenesis
Genetic
Umbilical Cord
Transcriptome
Mice
Osteogenesis
Transforming Growth Factor beta
Molecular Cell Biology
Basic Cancer Research
RNA
Small Interfering
lcsh:Science
Oligonucleotide Array Sequence Analysis
Multidisciplinary
Stem Cells
Cell Differentiation
Cell biology
Oncology
Bone Morphogenetic Proteins
Medicine
Cellular Types
Chemokines
Signal transduction
Stem cell
Chondrogenesis
Research Article
Signal Transduction
Nerve Tissue Proteins
Biology
Chondrocytes
Animals
Humans
Gene Silencing
Progenitor cell
Homeodomain Proteins
Osteoblasts
Multipotent Stem Cells
Mesenchymal stem cell
lcsh:R
Mesenchymal Stem Cells
Transforming growth factor beta
Molecular biology
Fibroblast Growth Factors
Cytoskeletal Proteins
Multipotent Stem Cell
biology.protein
lcsh:Q
Octamer Transcription Factor-3
Developmental Biology
Zdroj: PLoS ONE, Vol 8, Iss 7, p e67896 (2013)
PLoS ONE
ISSN: 1932-6203
Popis: BRE is a multifunctional adapter protein involved in DNA repair, cell survival and stress response. To date, most studies of this protein have been focused in the tumor model. The role of BRE in stem cell biology has never been investigated. Therefore, we have used HUCPV progenitor cells to elucidate the function of BRE. HUCPV cells are multipotent fetal progenitor cells which possess the ability to differentiate into a multitude of mesenchymal cell lineages when chemically induced and can be more easily amplified in culture. In this study, we have established that BRE expression was normally expressed in HUCPV cells but become down-regulated when the cells were induced to differentiate. In addition, silencing BRE expression, using BRE-siRNAs, in HUCPV cells could accelerate induced chondrogenic and osteogenic differentiation. Hence, we postulated that BRE played an important role in maintaining the stemness of HUCPV cells. We used microarray analysis to examine the transcriptome of BRE-silenced cells. BRE-silencing negatively regulated OCT4, FGF5 and FOXO1A. BRE-silencing also altered the expression of epigenetic genes and components of the TGF-β/BMP and FGF signaling pathways which are crucially involved in maintaining stem cell self-renewal. Comparative proteomic profiling also revealed that BRE-silencing resulted in decreased expressions of actin-binding proteins. In sum, we propose that BRE acts like an adaptor protein that promotes stemness and at the same time inhibits the differentiation of HUCPV cells.
Databáze: OpenAIRE
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