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

Tareq Hossan, Sankari Nagarajan, Simon J. Baumgart, Wanhua Xie, Roberto Tirado Magallanes, Céline Hernandez, Pierre Marie Chiaroni, Daniela Indenbirken, Melanie Spitzner, Morgane Thomas-Chollier, Marian Grade, Denis Thieffry, Adam Grundhoff, Florian Wegwitz, Steven Johnsen

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1369-1376
Number of pages8
JournalStem Cells
Volume34
Issue number5
DOIs
StatePublished - May 1 2016
Externally publishedYes

Keywords

  • Histone chaperone
  • Osteoblast differentiation
  • Structure specific recognition protein
  • Wnt signaling

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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  • Cite this

    Hossan, T., Nagarajan, S., Baumgart, S. J., Xie, W., Magallanes, R. T., Hernandez, C., Chiaroni, P. M., Indenbirken, D., Spitzner, M., Thomas-Chollier, M., Grade, M., Thieffry, D., Grundhoff, A., Wegwitz, F., & Johnsen, S. (2016). Histone Chaperone SSRP1 is Essential for Wnt Signaling Pathway Activity During Osteoblast Differentiation. Stem Cells, 34(5), 1369-1376. https://doi.org/10.1002/stem.2287