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Transcription factor ZNF25 is associated with osteoblast differentiation of human skeletal stem cells
- Source :
- BMC Genomics, Twine, N A, Harkness, L, Kassem, M & Wilkins, M R 2016, ' Transcription factor ZNF25 is associated with osteoblast differentiation of human skeletal stem cells ', BMC Genomics, vol. 17, 872 . https://doi.org/10.1186/s12864-016-3214-0
- Publisher :
- Springer Nature
-
Abstract
- BackgroundThe differentiation of human bone marrow derived skeletal stem cells (known as human bone marrow stromal or mesenchymal stem cells, hMSCs) into osteoblasts involves the activation of a small number of well-described transcription factors. To identify additional osteoblastic transcription factors, we studied gene expression of hMSCs during ex vivo osteoblast differentiation.ResultsClustering of gene expression, and literature investigation, revealed three transcription factors of interest – ZNF25, ZNF608 and ZBTB38. siRNA knockdown of ZNF25 resulted in significant suppression of alkaline phosphatase (ALP) activity. This effect was not present for ZNF608 and ZBTB38. To identify possible target genes of ZNF25, we analyzed gene expression following ZNF25 siRNA knockdown. This revealed a 23-fold upregulation of matrix metallopeptidase 1 and an 18-fold upregulation of leucine-rich repeat containing G protein-coupled receptor 5 and RAN-binding protein 3-like. We also observed enrichment in extracellular matrix organization, skeletal system development and regulation of ossification in the entire upregulated set of genes. Consistent with its function as a transcription factor during osteoblast differentiation of hMSC, we showed that the ZNF25 protein exhibits nuclear localization and is expressed in osteoblastic and osteocytic cells in vivo. ZNF25 is conserved in tetrapod vertebrates and contains a KRAB (Krueppel-associated box) transcriptional repressor domain.ConclusionsThis study shows that the uncharacterized transcription factor, ZNF25, is associated with differentiation of hMSC to osteoblasts.
- Subjects :
- 0301 basic medicine
Cellular differentiation
Cell Differentiation/genetics
Transcription Factors/genetics
Gene Expression
Biology
Evolution, Molecular
03 medical and health sciences
Calcification, Physiologic
Osteogenesis
Gene expression
medicine
Genetics
Human transcription factors
Animals
Humans
Transcription factor
Telomerase
Osteoblasts
Mesenchymal Stem Cells/cytology
Gene Expression Profiling
Mesenchymal stem cell
Osteoblasts/cytology
Osteoblast
Cell Differentiation
Mesenchymal Stem Cells
Zinc Fingers
ZNF25
Alkaline Phosphatase
Molecular biology
Telomerase/genetics
Gene expression profiling
030104 developmental biology
medicine.anatomical_structure
Alkaline Phosphatase/metabolism
Osteogenesis/genetics
Gene Knockdown Techniques
Multigene Family
Vertebrates
Mesenchymal stem cells
Stem cell
Extracellular matrix organization
Research Article
Transcription Factors
Biotechnology
Subjects
Details
- Language :
- English
- ISSN :
- 14712164
- Volume :
- 17
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- BMC Genomics
- Accession number :
- edsair.doi.dedup.....9a48240f314d2cfe748f4866033d3949
- Full Text :
- https://doi.org/10.1186/s12864-016-3214-0