Phosphoproteomic profiling reveals a defined genetic program for osteoblastic lineage commitment of human bone marrow-derived stromal stem cells.
- Barrio-Hernandez I Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark.
- Jafari A Department of Endocrinology and Metabolism, University Hospital of Odense and University of Southern Denmark, 5000 Odense C, Denmark.
- Rigbolt KTG Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark.
- Hallenborg P Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark.
- Sanchez-Quiles V Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark.
- Skovrind I Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark.
- Akimov V Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark.
- Kratchmarova I Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark.
- Dengjel J Department of Biology, University of Fribourg, 1700 Fribourg, Switzerland.
- Kassem M Department of Endocrinology and Metabolism, University Hospital of Odense and University of Southern Denmark, 5000 Odense C, Denmark.
- Blagoev B Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark.
- 2019-12-14
Published in:
- Genome research. - 2020
Cell Differentiation
Humans
Mesenchymal Stem Cells
Osteoblasts
Phosphoproteins
Phylogeny
Proteome
Proteomics
English
Bone marrow-derived mesenchymal stem cells (MSCs) differentiate into osteoblasts upon stimulation by signals present in their niche. Because the global signaling cascades involved in the early phases of MSCs osteoblast (OB) differentiation are not well-defined, we used quantitative mass spectrometry to delineate changes in human MSCs proteome and phosphoproteome during the first 24 h of their OB lineage commitment. The temporal profiles of 6252 proteins and 15,059 phosphorylation sites suggested at least two distinct signaling waves: one peaking within 30 to 60 min after stimulation and a second upsurge after 24 h. In addition to providing a comprehensive view of the proteome and phosphoproteome dynamics during early MSCs differentiation, our analyses identified a key role of serine/threonine protein kinase D1 (PRKD1) in OB commitment. At the onset of OB differentiation, PRKD1 initiates activation of the pro-osteogenic transcription factor RUNX2 by triggering phosphorylation and nuclear exclusion of the histone deacetylase HDAC7.
- Language
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- English
- Open access status
- hybrid
- Identifiers
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- DOI 10.1101/gr.248286.119
- PMID 31831592
- Persistent URL
- https://sonar.ch/global/documents/138924
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