A Systems-level Characterization of the Differentiation of Human Embryonic Stem Cells into Mesenchymal Stem Cells*[S]
<p dir="ltr">Mesenchymal stem/stromal cells (MSCs) are self-renewing multipotent cells with regenerative, secretory and immunomodulatory capabilities that are beneficial for the treatment of various diseases. To avoid the issues that come with using tissue-derived MSCs in therapy, MS...
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2019
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| _version_ | 1864513511430815744 |
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| author | Anja M. Billing (1297773) |
| author2 | Shaima S. Dib (1297767) Aditya M. Bhagwat (14152806) Israel T. da Silva (12274334) Rodrigo D. Drummond (17430056) Shahina Hayat (8774135) Rasha Al-Mismar (1297782) Hisham Ben-Hamidane (18808291) Neha Goswami (9500432) Kasper Engholm-Keller (1297761) Martin R. Larsen (375762) Karsten Suhre (67967) Arash Rafii (102768) Johannes Graumann (1297758) |
| author2_role | author author author author author author author author author author author author author |
| author_facet | Anja M. Billing (1297773) Shaima S. Dib (1297767) Aditya M. Bhagwat (14152806) Israel T. da Silva (12274334) Rodrigo D. Drummond (17430056) Shahina Hayat (8774135) Rasha Al-Mismar (1297782) Hisham Ben-Hamidane (18808291) Neha Goswami (9500432) Kasper Engholm-Keller (1297761) Martin R. Larsen (375762) Karsten Suhre (67967) Arash Rafii (102768) Johannes Graumann (1297758) |
| author_role | author |
| dc.creator.none.fl_str_mv | Anja M. Billing (1297773) Shaima S. Dib (1297767) Aditya M. Bhagwat (14152806) Israel T. da Silva (12274334) Rodrigo D. Drummond (17430056) Shahina Hayat (8774135) Rasha Al-Mismar (1297782) Hisham Ben-Hamidane (18808291) Neha Goswami (9500432) Kasper Engholm-Keller (1297761) Martin R. Larsen (375762) Karsten Suhre (67967) Arash Rafii (102768) Johannes Graumann (1297758) |
| dc.date.none.fl_str_mv | 2019-10-19T06:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1074/mcp.ra119.001356 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/A_Systems-level_Characterization_of_the_Differentiation_of_Human_Embryonic_Stem_Cells_into_Mesenchymal_Stem_Cells_S_/26019478 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Biochemistry and cell biology Biomedical and clinical sciences Medical biochemistry and metabolomics Medical biotechnology Mesenchymal stem/stromal cells Embryonic stem cells Cell-based therapy Stem cell biology Noncoding RNAs |
| dc.title.none.fl_str_mv | A Systems-level Characterization of the Differentiation of Human Embryonic Stem Cells into Mesenchymal Stem Cells*[S] |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Mesenchymal stem/stromal cells (MSCs) are self-renewing multipotent cells with regenerative, secretory and immunomodulatory capabilities that are beneficial for the treatment of various diseases. To avoid the issues that come with using tissue-derived MSCs in therapy, MSCs may be generated by the differentiation of human embryonic stems cells (hESCs) in culture. However, the changes that occur during the differentiation process have not been comprehensively characterized. Here, we combined transcriptome, proteome and phosphoproteome profiling to perform an in-depth, multi-omics study of the hESCs-to-MSCs differentiation process. Based on RNA-to-protein correlation, we determined a set of high confidence genes that are important to differentiation. Among the earliest and strongest induced proteins with extensive differential phosphorylation was AHNAK, which we hypothesized to be a defining factor in MSC biology. We observed two distinct expression waves of developmental HOX genes and an AGO2-to-AGO3 switch in gene silencing. Exploring the kinetic of noncoding ORFs during differentiation, we mapped new functions to well annotated long noncoding RNAs (CARMN, MALAT, NEAT1, LINC00152) as well as new candidates which we identified to be important to the differentiation process. Phosphoproteome analysis revealed ESC and MSC-specific phosphorylation motifs with PAK2 and RAF1 as top predicted upstream kinases in MSCs. Our data represent a rich systems-level resource on ESC-to-MSC differentiation that will be useful for the study of stem cell biology.</p><h2>Other Information</h2><p dir="ltr">Published in: Molecular & Cellular Proteomics<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1074/mcp.ra119.001356" target="_blank">https://dx.doi.org/10.1074/mcp.ra119.001356</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_328e45160cc3e02559625c3fbfcee3d1 |
| identifier_str_mv | 10.1074/mcp.ra119.001356 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/26019478 |
| publishDate | 2019 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | A Systems-level Characterization of the Differentiation of Human Embryonic Stem Cells into Mesenchymal Stem Cells*[S]Anja M. Billing (1297773)Shaima S. Dib (1297767)Aditya M. Bhagwat (14152806)Israel T. da Silva (12274334)Rodrigo D. Drummond (17430056)Shahina Hayat (8774135)Rasha Al-Mismar (1297782)Hisham Ben-Hamidane (18808291)Neha Goswami (9500432)Kasper Engholm-Keller (1297761)Martin R. Larsen (375762)Karsten Suhre (67967)Arash Rafii (102768)Johannes Graumann (1297758)Biological sciencesBiochemistry and cell biologyBiomedical and clinical sciencesMedical biochemistry and metabolomicsMedical biotechnologyMesenchymal stem/stromal cellsEmbryonic stem cellsCell-based therapyStem cell biologyNoncoding RNAs<p dir="ltr">Mesenchymal stem/stromal cells (MSCs) are self-renewing multipotent cells with regenerative, secretory and immunomodulatory capabilities that are beneficial for the treatment of various diseases. To avoid the issues that come with using tissue-derived MSCs in therapy, MSCs may be generated by the differentiation of human embryonic stems cells (hESCs) in culture. However, the changes that occur during the differentiation process have not been comprehensively characterized. Here, we combined transcriptome, proteome and phosphoproteome profiling to perform an in-depth, multi-omics study of the hESCs-to-MSCs differentiation process. Based on RNA-to-protein correlation, we determined a set of high confidence genes that are important to differentiation. Among the earliest and strongest induced proteins with extensive differential phosphorylation was AHNAK, which we hypothesized to be a defining factor in MSC biology. We observed two distinct expression waves of developmental HOX genes and an AGO2-to-AGO3 switch in gene silencing. Exploring the kinetic of noncoding ORFs during differentiation, we mapped new functions to well annotated long noncoding RNAs (CARMN, MALAT, NEAT1, LINC00152) as well as new candidates which we identified to be important to the differentiation process. Phosphoproteome analysis revealed ESC and MSC-specific phosphorylation motifs with PAK2 and RAF1 as top predicted upstream kinases in MSCs. Our data represent a rich systems-level resource on ESC-to-MSC differentiation that will be useful for the study of stem cell biology.</p><h2>Other Information</h2><p dir="ltr">Published in: Molecular & Cellular Proteomics<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1074/mcp.ra119.001356" target="_blank">https://dx.doi.org/10.1074/mcp.ra119.001356</a></p>2019-10-19T06:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1074/mcp.ra119.001356https://figshare.com/articles/journal_contribution/A_Systems-level_Characterization_of_the_Differentiation_of_Human_Embryonic_Stem_Cells_into_Mesenchymal_Stem_Cells_S_/26019478CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/260194782019-10-19T06:00:00Z |
| spellingShingle | A Systems-level Characterization of the Differentiation of Human Embryonic Stem Cells into Mesenchymal Stem Cells*[S] Anja M. Billing (1297773) Biological sciences Biochemistry and cell biology Biomedical and clinical sciences Medical biochemistry and metabolomics Medical biotechnology Mesenchymal stem/stromal cells Embryonic stem cells Cell-based therapy Stem cell biology Noncoding RNAs |
| status_str | publishedVersion |
| title | A Systems-level Characterization of the Differentiation of Human Embryonic Stem Cells into Mesenchymal Stem Cells*[S] |
| title_full | A Systems-level Characterization of the Differentiation of Human Embryonic Stem Cells into Mesenchymal Stem Cells*[S] |
| title_fullStr | A Systems-level Characterization of the Differentiation of Human Embryonic Stem Cells into Mesenchymal Stem Cells*[S] |
| title_full_unstemmed | A Systems-level Characterization of the Differentiation of Human Embryonic Stem Cells into Mesenchymal Stem Cells*[S] |
| title_short | A Systems-level Characterization of the Differentiation of Human Embryonic Stem Cells into Mesenchymal Stem Cells*[S] |
| title_sort | A Systems-level Characterization of the Differentiation of Human Embryonic Stem Cells into Mesenchymal Stem Cells*[S] |
| topic | Biological sciences Biochemistry and cell biology Biomedical and clinical sciences Medical biochemistry and metabolomics Medical biotechnology Mesenchymal stem/stromal cells Embryonic stem cells Cell-based therapy Stem cell biology Noncoding RNAs |