Transcription factor ZNF25 is associated with osteoblast differentiation of human skeletal stem cells

Natalie A. Twine, Linda Harkness, Moustapha Kassem, Marc R. Wilkins

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Abstrakt

Background

The 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.

Results

Clustering 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.

Conclusions

This study shows that the uncharacterized transcription factor, ZNF25, is associated with differentiation of hMSC to osteoblasts.
OriginalsprogEngelsk
Artikelnummer872
TidsskriftBMC Genomics
Vol/bind17
Antal sider15
ISSN1471-2164
DOI
StatusUdgivet - 2016

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