Histone Chaperone SSRP1 is Essential for Wnt Signaling Pathway Activity During Osteoblast Differentiation

Stem Cells. 2016 May;34(5):1369-76. doi: 10.1002/stem.2287. Epub 2016 Feb 13.


Cellular differentiation is accompanied by dramatic changes in chromatin structure which direct the activation of lineage-specific transcriptional programs. Structure-specific recognition protein-1 (SSRP1) is a histone chaperone which is important for chromatin-associated processes such as transcription, DNA replication and repair. Since the function of SSRP1 during cell differentiation remains unclear, we investigated its potential role in controlling lineage determination. Depletion of SSRP1 in human mesenchymal stem cells elicited lineage-specific effects by increasing expression of adipocyte-specific genes and decreasing the expression of osteoblast-specific genes. Consistent with a role in controlling lineage specification, transcriptome-wide RNA-sequencing following SSRP1 depletion and the induction of osteoblast differentiation revealed a specific decrease in the expression of genes involved in biological processes related to osteoblast differentiation. Importantly, we observed a specific downregulation of target genes of the canonical Wnt signaling pathway, which was accompanied by decreased nuclear localization of active β-catenin. Together our data uncover a previously unknown role for SSRP1 in promoting the activation of the Wnt signaling pathway activity during cellular differentiation. Stem Cells 2016;34:1369-1376.

Keywords: Histone chaperone; Osteoblast differentiation; Structure specific recognition protein; Wnt signaling.

MeSH terms

  • Adipocytes / cytology
  • Adipocytes / metabolism
  • Cell Differentiation* / genetics
  • Cell Line
  • Cell Nucleus / metabolism
  • DNA-Binding Proteins / metabolism*
  • Gene Deletion
  • Gene Expression Regulation
  • High Mobility Group Proteins / metabolism*
  • Histone Chaperones / metabolism*
  • Humans
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • Osteoblasts / cytology*
  • Osteoblasts / metabolism*
  • Protein Transport
  • Reproducibility of Results
  • Transcriptional Elongation Factors / metabolism*
  • Wnt Signaling Pathway* / genetics
  • beta Catenin / metabolism


  • DNA-Binding Proteins
  • High Mobility Group Proteins
  • Histone Chaperones
  • SSRP1 protein, human
  • Transcriptional Elongation Factors
  • beta Catenin