Phosphoproteomic profiling reveals a defined genetic program for osteoblastic lineage commitment of human bone marrow–derived stromal stem cells

Barrio-Hernandez, Inigo; Jafari, Abbas; Rigbolt, Kristoffer T.G.; Hallenborg, Philip; Sanchez-Quiles, Virginia; Skovrind, Ida; Akimov, Vyacheslav; Kratchmarova, Irina; Dengjel, Jörn; Kassem, Moustapha; Blagoev, Blagoy

doi:10.1101/gr.248286.119

Back

Journal article

+ 6 other files

Phosphoproteomic profiling reveals a defined genetic program for osteoblastic lineage commitment of human bone marrow–derived stromal stem cells

Barrio-Hernandez, Inigo Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M, Denmark
Jafari, Abbas Department of Endocrinology and Metabolism, University Hospital of Odense and University of Southern Denmark, Odense C, Denmark
Rigbolt, Kristoffer T.G. Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M, Denmark
Hallenborg, Philip Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M, Denmark
Sanchez-Quiles, Virginia Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M, Denmark
Skovrind, Ida Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M, Denmark
Akimov, Vyacheslav Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M, Denmark
Kratchmarova, Irina Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M, Denmark
Dengjel, Jörn Department of Biology, University of Fribourg, Switzerland
Kassem, Moustapha Department of Endocrinology and Metabolism, University Hospital of Odense and University of Southern Denmark, Odense C, Denmark
Blagoev, Blagoy Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M, Denmark

01.01.2020

Published in:

Genome Research. - 2020, vol. 30, no. 1, p. 127-137

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.

Faculty

Faculté des sciences et de médecine

Department

Département de Biologie

Language