title: Histone Chaperone SSRP1 is Essential for Wnt Signaling Pathway Activity During Osteoblast Differentiation.
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. Stem Cells 2016;34:1369-1376.
authors.affiliation: Department of General, Visceral and Pediatric Surgery, Göttingen Center for Molecular Biosciences (GZMB), University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Tareq
authors.initials: T
authors.lastname: Hossan
authors.affiliation: Department of General, Visceral and Pediatric Surgery, Göttingen Center for Molecular Biosciences (GZMB), University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Sankari
authors.initials: S
authors.lastname: Nagarajan
authors.affiliation: Department of General, Visceral and Pediatric Surgery, Göttingen Center for Molecular Biosciences (GZMB), University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Baumgart
authors.affiliation: Department of General, Visceral and Pediatric Surgery, Göttingen Center for Molecular Biosciences (GZMB), University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Wanhua
authors.initials: W
authors.lastname: Xie
authors.affiliation: Computational Systems Biology Team, Institut de Biologie de l'Ecole Normale Supérieure (IBENS), CNRS, Inserm, Ecole Normale Supérieure, PSL Research University, Paris, France.
authors.forename: Roberto Tirado
authors.initials: RT
authors.lastname: Magallanes
authors.affiliation: Computational Systems Biology Team, Institut de Biologie de l'Ecole Normale Supérieure (IBENS), CNRS, Inserm, Ecole Normale Supérieure, PSL Research University, Paris, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Hernandez
authors.affiliation: Computational Systems Biology Team, Institut de Biologie de l'Ecole Normale Supérieure (IBENS), CNRS, Inserm, Ecole Normale Supérieure, PSL Research University, Paris, France.
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Chiaroni
authors.affiliation: Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Indenbirken
authors.affiliation: Department of General, Visceral and Pediatric Surgery, Göttingen Center for Molecular Biosciences (GZMB), University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Spitzner
authors.affiliation: Computational Systems Biology Team, Institut de Biologie de l'Ecole Normale Supérieure (IBENS), CNRS, Inserm, Ecole Normale Supérieure, PSL Research University, Paris, France.
authors.forename: Morgane
authors.initials: M
authors.lastname: Thomas-Chollier
authors.affiliation: Department of General, Visceral and Pediatric Surgery, Göttingen Center for Molecular Biosciences (GZMB), University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Marian
authors.initials: M
authors.lastname: Grade
authors.affiliation: Computational Systems Biology Team, Institut de Biologie de l'Ecole Normale Supérieure (IBENS), CNRS, Inserm, Ecole Normale Supérieure, PSL Research University, Paris, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Thieffry
authors.affiliation: Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
authors.forename: Adam
authors.initials: A
authors.lastname: Grundhoff
authors.affiliation: Department of General, Visceral and Pediatric Surgery, Göttingen Center for Molecular Biosciences (GZMB), University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Wegwitz
authors.affiliation: Department of General, Visceral and Pediatric Surgery, Göttingen Center for Molecular Biosciences (GZMB), University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Johnsen
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006609:High Mobility Group Proteins / Q000378:metabolism*; D056488:Histone Chaperones / Q000378:metabolism*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism*; D021381:Protein Transport; D015203:Reproducibility of Results; D035602:Transcriptional Elongation Factors / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000235:genetics; D051176:beta Catenin / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D056488:Histone Chaperones; C073537:SSRP1 protein, human; D035602:Transcriptional Elongation Factors; D051176:beta Catenin
keywords: Histone chaperone; Osteoblast differentiation; Structure specific recognition protein; Wnt signaling