Protein Expression of AEBP1, MCM4, and FABP4 Differentiate Osteogenic, Adipogenic, and Mesenchymal Stromal Stem Cells
Mesenchymal stem cells (MSCs) gain an increasing focus in the field of regenerative medicine due to their differentiation abilities into chondrocytes, adipocytes, and osteoblastic cells. However, it is apparent that the transformation processes are extremely complex and cause cellular heterogeneity....
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-02-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/5/2568 |
| _version_ | 1797474998181429248 |
|---|---|
| author | Thorben Sauer Giulia Facchinetti Michael Kohl Justyna M. Kowal Svitlana Rozanova Julia Horn Hagen Schmal Ivo Kwee Arndt-Peter Schulz Sonja Hartwig Moustapha Kassem Jens K. Habermann Timo Gemoll |
| author_facet | Thorben Sauer Giulia Facchinetti Michael Kohl Justyna M. Kowal Svitlana Rozanova Julia Horn Hagen Schmal Ivo Kwee Arndt-Peter Schulz Sonja Hartwig Moustapha Kassem Jens K. Habermann Timo Gemoll |
| author_sort | Thorben Sauer |
| collection | DOAJ |
| description | Mesenchymal stem cells (MSCs) gain an increasing focus in the field of regenerative medicine due to their differentiation abilities into chondrocytes, adipocytes, and osteoblastic cells. However, it is apparent that the transformation processes are extremely complex and cause cellular heterogeneity. The study aimed to characterize differences between MSCs and cells after adipogenic (AD) or osteoblastic (OB) differentiation at the proteome level. Comparative proteomic profiling was performed using tandem mass spectrometry in data-independent acquisition mode. Proteins were quantified by deep neural networks in library-free mode and correlated to the Molecular Signature Database (MSigDB) hallmark gene set collections for functional annotation. We analyzed 4108 proteins across all samples, which revealed a distinct clustering between MSCs and cell differentiation states. Protein expression profiling identified activation of the <i>Peroxisome proliferator-activated receptors (PPARs)</i> signaling pathway after AD. In addition, two distinct protein marker panels could be defined for osteoblastic and adipocytic cell lineages. Hereby, overexpression of AEBP1 and MCM4 for OB as well as of FABP4 for AD was detected as the most promising molecular markers. Combination of deep neural network and machine-learning algorithms with data-independent mass spectrometry distinguish MSCs and cell lineages after adipogenic or osteoblastic differentiation. We identified specific proteins as the molecular basis for bone formation, which could be used for regenerative medicine in the future. |
| first_indexed | 2024-03-09T20:37:53Z |
| format | Article |
| id | doaj.art-6ad5eb6590ee4ebe9f2fa93bb3d91a95 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T20:37:53Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-6ad5eb6590ee4ebe9f2fa93bb3d91a952023-11-23T23:06:08ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-02-01235256810.3390/ijms23052568Protein Expression of AEBP1, MCM4, and FABP4 Differentiate Osteogenic, Adipogenic, and Mesenchymal Stromal Stem CellsThorben Sauer0Giulia Facchinetti1Michael Kohl2Justyna M. Kowal3Svitlana Rozanova4Julia Horn5Hagen Schmal6Ivo Kwee7Arndt-Peter Schulz8Sonja Hartwig9Moustapha Kassem10Jens K. Habermann11Timo Gemoll12Section for Translational Surgical Oncology and Biobanking, Department of Surgery, University Hospital Schleswig-Holstein, University of Luebeck, Campus Luebeck, Ratzeburger Allee 160, 23562 Luebeck, GermanySection for Translational Surgical Oncology and Biobanking, Department of Surgery, University Hospital Schleswig-Holstein, University of Luebeck, Campus Luebeck, Ratzeburger Allee 160, 23562 Luebeck, GermanySection for Translational Surgical Oncology and Biobanking, Department of Surgery, University Hospital Schleswig-Holstein, University of Luebeck, Campus Luebeck, Ratzeburger Allee 160, 23562 Luebeck, GermanyDepartment of Endocrinology and Metabolism, University Hospital of Odense, J.B. Winsløws Vej 25, 5230 Odense, DenmarkSection for Translational Surgical Oncology and Biobanking, Department of Surgery, University Hospital Schleswig-Holstein, University of Luebeck, Campus Luebeck, Ratzeburger Allee 160, 23562 Luebeck, GermanySection for Translational Surgical Oncology and Biobanking, Department of Surgery, University Hospital Schleswig-Holstein, University of Luebeck, Campus Luebeck, Ratzeburger Allee 160, 23562 Luebeck, GermanyDepartment of Orthopedics and Traumatology, Odense University Hospital, Odense, J.B. Winsløws Vej 4, 5000 Odense, DenmarkBigOmics Analytics SA, 6500 Bellinzona, SwitzerlandFraunhofer Research Institution for Individualized and Cell-Based Medical Engineering Luebeck, Moenkhofer Weg 239a, 23562 Luebeck, GermanyGerman Center for Diabetes Research (DZD), 85764 Muenchen, GermanyDepartment of Endocrinology and Metabolism, University Hospital of Odense, J.B. Winsløws Vej 25, 5230 Odense, DenmarkSection for Translational Surgical Oncology and Biobanking, Department of Surgery, University Hospital Schleswig-Holstein, University of Luebeck, Campus Luebeck, Ratzeburger Allee 160, 23562 Luebeck, GermanySection for Translational Surgical Oncology and Biobanking, Department of Surgery, University Hospital Schleswig-Holstein, University of Luebeck, Campus Luebeck, Ratzeburger Allee 160, 23562 Luebeck, GermanyMesenchymal stem cells (MSCs) gain an increasing focus in the field of regenerative medicine due to their differentiation abilities into chondrocytes, adipocytes, and osteoblastic cells. However, it is apparent that the transformation processes are extremely complex and cause cellular heterogeneity. The study aimed to characterize differences between MSCs and cells after adipogenic (AD) or osteoblastic (OB) differentiation at the proteome level. Comparative proteomic profiling was performed using tandem mass spectrometry in data-independent acquisition mode. Proteins were quantified by deep neural networks in library-free mode and correlated to the Molecular Signature Database (MSigDB) hallmark gene set collections for functional annotation. We analyzed 4108 proteins across all samples, which revealed a distinct clustering between MSCs and cell differentiation states. Protein expression profiling identified activation of the <i>Peroxisome proliferator-activated receptors (PPARs)</i> signaling pathway after AD. In addition, two distinct protein marker panels could be defined for osteoblastic and adipocytic cell lineages. Hereby, overexpression of AEBP1 and MCM4 for OB as well as of FABP4 for AD was detected as the most promising molecular markers. Combination of deep neural network and machine-learning algorithms with data-independent mass spectrometry distinguish MSCs and cell lineages after adipogenic or osteoblastic differentiation. We identified specific proteins as the molecular basis for bone formation, which could be used for regenerative medicine in the future.https://www.mdpi.com/1422-0067/23/5/2568protein profilingdata-independent acquisition mass spectrometrySWATHhuman stromal/mesenchymal stem cellsdifferentiation markersmachine learning |
| spellingShingle | Thorben Sauer Giulia Facchinetti Michael Kohl Justyna M. Kowal Svitlana Rozanova Julia Horn Hagen Schmal Ivo Kwee Arndt-Peter Schulz Sonja Hartwig Moustapha Kassem Jens K. Habermann Timo Gemoll Protein Expression of AEBP1, MCM4, and FABP4 Differentiate Osteogenic, Adipogenic, and Mesenchymal Stromal Stem Cells International Journal of Molecular Sciences protein profiling data-independent acquisition mass spectrometry SWATH human stromal/mesenchymal stem cells differentiation markers machine learning |
| title | Protein Expression of AEBP1, MCM4, and FABP4 Differentiate Osteogenic, Adipogenic, and Mesenchymal Stromal Stem Cells |
| title_full | Protein Expression of AEBP1, MCM4, and FABP4 Differentiate Osteogenic, Adipogenic, and Mesenchymal Stromal Stem Cells |
| title_fullStr | Protein Expression of AEBP1, MCM4, and FABP4 Differentiate Osteogenic, Adipogenic, and Mesenchymal Stromal Stem Cells |
| title_full_unstemmed | Protein Expression of AEBP1, MCM4, and FABP4 Differentiate Osteogenic, Adipogenic, and Mesenchymal Stromal Stem Cells |
| title_short | Protein Expression of AEBP1, MCM4, and FABP4 Differentiate Osteogenic, Adipogenic, and Mesenchymal Stromal Stem Cells |
| title_sort | protein expression of aebp1 mcm4 and fabp4 differentiate osteogenic adipogenic and mesenchymal stromal stem cells |
| topic | protein profiling data-independent acquisition mass spectrometry SWATH human stromal/mesenchymal stem cells differentiation markers machine learning |
| url | https://www.mdpi.com/1422-0067/23/5/2568 |
| work_keys_str_mv | AT thorbensauer proteinexpressionofaebp1mcm4andfabp4differentiateosteogenicadipogenicandmesenchymalstromalstemcells AT giuliafacchinetti proteinexpressionofaebp1mcm4andfabp4differentiateosteogenicadipogenicandmesenchymalstromalstemcells AT michaelkohl proteinexpressionofaebp1mcm4andfabp4differentiateosteogenicadipogenicandmesenchymalstromalstemcells AT justynamkowal proteinexpressionofaebp1mcm4andfabp4differentiateosteogenicadipogenicandmesenchymalstromalstemcells AT svitlanarozanova proteinexpressionofaebp1mcm4andfabp4differentiateosteogenicadipogenicandmesenchymalstromalstemcells AT juliahorn proteinexpressionofaebp1mcm4andfabp4differentiateosteogenicadipogenicandmesenchymalstromalstemcells AT hagenschmal proteinexpressionofaebp1mcm4andfabp4differentiateosteogenicadipogenicandmesenchymalstromalstemcells AT ivokwee proteinexpressionofaebp1mcm4andfabp4differentiateosteogenicadipogenicandmesenchymalstromalstemcells AT arndtpeterschulz proteinexpressionofaebp1mcm4andfabp4differentiateosteogenicadipogenicandmesenchymalstromalstemcells AT sonjahartwig proteinexpressionofaebp1mcm4andfabp4differentiateosteogenicadipogenicandmesenchymalstromalstemcells AT moustaphakassem proteinexpressionofaebp1mcm4andfabp4differentiateosteogenicadipogenicandmesenchymalstromalstemcells AT jenskhabermann proteinexpressionofaebp1mcm4andfabp4differentiateosteogenicadipogenicandmesenchymalstromalstemcells AT timogemoll proteinexpressionofaebp1mcm4andfabp4differentiateosteogenicadipogenicandmesenchymalstromalstemcells |