Quiescence, Stemness and Adipogenic Differentiation Capacity in Human DLK1<sup>−</sup>/CD34<sup>+</sup>/CD24<sup>+</sup> Adipose Stem/Progenitor Cells
We explore the status of quiescence, stemness and adipogenic differentiation capacity in adipose stem/progenitor cells (ASCs) ex vivo, immediately after isolation from human subcutaneous white adipose tissue, by sorting the stromal vascular fraction into cell-surface DLK1<sup>+</sup>/CD3...
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MDPI AG
2021-01-01
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| Online Access: | https://www.mdpi.com/2073-4409/10/2/214 |
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| author | Florian M. Hatzmann Asim Ejaz G. Jan Wiegers Markus Mandl Camille Brucker Stefan Lechner Tina Rauchenwald Marit Zwierzina Saphira Baumgarten Sonja Wagner Monika Mattesich Petra Waldegger Gerhard Pierer Werner Zwerschke |
| author_facet | Florian M. Hatzmann Asim Ejaz G. Jan Wiegers Markus Mandl Camille Brucker Stefan Lechner Tina Rauchenwald Marit Zwierzina Saphira Baumgarten Sonja Wagner Monika Mattesich Petra Waldegger Gerhard Pierer Werner Zwerschke |
| author_sort | Florian M. Hatzmann |
| collection | DOAJ |
| description | We explore the status of quiescence, stemness and adipogenic differentiation capacity in adipose stem/progenitor cells (ASCs) ex vivo, immediately after isolation from human subcutaneous white adipose tissue, by sorting the stromal vascular fraction into cell-surface DLK1<sup>+</sup>/CD34<sup>−</sup>, DLK1<sup>+</sup>/CD34<sup>dim</sup> and DLK1<sup>−</sup>/CD34<sup>+</sup> cells. We demonstrate that DLK1<sup>−</sup>/CD34<sup>+</sup> cells, the only population exhibiting proliferative and adipogenic capacity, express ex vivo the bonafide quiescence markers p21<sup>Cip1</sup>, p27<sup>Kip1</sup> and p57<sup>Kip2</sup> but neither proliferation markers nor the senescence marker p16<sup>Ink4a</sup>. The pluripotency markers NANOG, SOX2 and OCT4 are barely detectable in ex vivo ASCs while the somatic stemness factors, c-MYC and KLF4 and the early adipogenic factor C/EBPβ are highly expressed. Further sorting of ASCs into DLK1<sup>−</sup>/CD34<sup>+</sup>/CD24<sup>−</sup> and DLK1<sup>−</sup>/CD34<sup>+</sup>/CD24<sup>+</sup> fractions shows that KLF4 and c-MYC are higher expressed in DLK1<sup>−</sup>/CD34<sup>+</sup>/CD24<sup>+</sup> cells correlating with higher colony formation capacity and considerably lower adipogenic activity. Proliferation capacity is similar in both populations. Next, we show that ASCs routinely isolated by plastic-adherence are DLK1<sup>−</sup>/CD34<sup>+</sup>/CD24<sup>+</sup>. Intriguingly, CD24 knock-down in these cells reduces proliferation and adipogenesis. In conclusion, DLK1<sup>−</sup>/CD34<sup>+</sup> ASCs in human sWAT exist in a quiescent state, express high levels of somatic stemness factors and the early adipogenic transcription factor C/EBPβ but senescence and pluripotency markers are barely detectable. Moreover, our data indicate that CD24 is necessary for adequate ASC proliferation and adipogenesis and that stemness is higher and adipogenic capacity lower in DLK1<sup>−</sup>/CD34<sup>+</sup>/CD24<sup>+</sup> relative to DLK1<sup>−</sup>/CD34<sup>+</sup>/CD24<sup>−</sup> subpopulations. |
| first_indexed | 2024-03-09T04:01:30Z |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-09T04:01:30Z |
| publishDate | 2021-01-01 |
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| series | Cells |
| spelling | doaj.art-6c5b49aa2b4c4af498332e175a64e09f2023-12-03T14:12:59ZengMDPI AGCells2073-44092021-01-0110221410.3390/cells10020214Quiescence, Stemness and Adipogenic Differentiation Capacity in Human DLK1<sup>−</sup>/CD34<sup>+</sup>/CD24<sup>+</sup> Adipose Stem/Progenitor CellsFlorian M. Hatzmann0Asim Ejaz1G. Jan Wiegers2Markus Mandl3Camille Brucker4Stefan Lechner5Tina Rauchenwald6Marit Zwierzina7Saphira Baumgarten8Sonja Wagner9Monika Mattesich10Petra Waldegger11Gerhard Pierer12Werner Zwerschke13Division of Cell Metabolism and Differentiation Research, Research Institute for Biomedical Aging Research, University of Innsbruck, Rennweg 10, A-6020 Innsbruck, AustriaDivision of Cell Metabolism and Differentiation Research, Research Institute for Biomedical Aging Research, University of Innsbruck, Rennweg 10, A-6020 Innsbruck, AustriaDivision of Developmental Immunology, Biocenter, Medical University of Innsbruck, Innrain 80-82, A-6020 Innsbruck, AustriaDivision of Cell Metabolism and Differentiation Research, Research Institute for Biomedical Aging Research, University of Innsbruck, Rennweg 10, A-6020 Innsbruck, AustriaDivision of Cell Metabolism and Differentiation Research, Research Institute for Biomedical Aging Research, University of Innsbruck, Rennweg 10, A-6020 Innsbruck, AustriaDivision of Cell Metabolism and Differentiation Research, Research Institute for Biomedical Aging Research, University of Innsbruck, Rennweg 10, A-6020 Innsbruck, AustriaDepartment of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Innsbruck, Anichstraße 35, A-6020 Innsbruck, AustriaDepartment of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Innsbruck, Anichstraße 35, A-6020 Innsbruck, AustriaDivision of Cell Metabolism and Differentiation Research, Research Institute for Biomedical Aging Research, University of Innsbruck, Rennweg 10, A-6020 Innsbruck, AustriaDivision of Cell Metabolism and Differentiation Research, Research Institute for Biomedical Aging Research, University of Innsbruck, Rennweg 10, A-6020 Innsbruck, AustriaDepartment of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Innsbruck, Anichstraße 35, A-6020 Innsbruck, AustriaDivision of Cell Metabolism and Differentiation Research, Research Institute for Biomedical Aging Research, University of Innsbruck, Rennweg 10, A-6020 Innsbruck, AustriaDepartment of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Innsbruck, Anichstraße 35, A-6020 Innsbruck, AustriaDivision of Cell Metabolism and Differentiation Research, Research Institute for Biomedical Aging Research, University of Innsbruck, Rennweg 10, A-6020 Innsbruck, AustriaWe explore the status of quiescence, stemness and adipogenic differentiation capacity in adipose stem/progenitor cells (ASCs) ex vivo, immediately after isolation from human subcutaneous white adipose tissue, by sorting the stromal vascular fraction into cell-surface DLK1<sup>+</sup>/CD34<sup>−</sup>, DLK1<sup>+</sup>/CD34<sup>dim</sup> and DLK1<sup>−</sup>/CD34<sup>+</sup> cells. We demonstrate that DLK1<sup>−</sup>/CD34<sup>+</sup> cells, the only population exhibiting proliferative and adipogenic capacity, express ex vivo the bonafide quiescence markers p21<sup>Cip1</sup>, p27<sup>Kip1</sup> and p57<sup>Kip2</sup> but neither proliferation markers nor the senescence marker p16<sup>Ink4a</sup>. The pluripotency markers NANOG, SOX2 and OCT4 are barely detectable in ex vivo ASCs while the somatic stemness factors, c-MYC and KLF4 and the early adipogenic factor C/EBPβ are highly expressed. Further sorting of ASCs into DLK1<sup>−</sup>/CD34<sup>+</sup>/CD24<sup>−</sup> and DLK1<sup>−</sup>/CD34<sup>+</sup>/CD24<sup>+</sup> fractions shows that KLF4 and c-MYC are higher expressed in DLK1<sup>−</sup>/CD34<sup>+</sup>/CD24<sup>+</sup> cells correlating with higher colony formation capacity and considerably lower adipogenic activity. Proliferation capacity is similar in both populations. Next, we show that ASCs routinely isolated by plastic-adherence are DLK1<sup>−</sup>/CD34<sup>+</sup>/CD24<sup>+</sup>. Intriguingly, CD24 knock-down in these cells reduces proliferation and adipogenesis. In conclusion, DLK1<sup>−</sup>/CD34<sup>+</sup> ASCs in human sWAT exist in a quiescent state, express high levels of somatic stemness factors and the early adipogenic transcription factor C/EBPβ but senescence and pluripotency markers are barely detectable. Moreover, our data indicate that CD24 is necessary for adequate ASC proliferation and adipogenesis and that stemness is higher and adipogenic capacity lower in DLK1<sup>−</sup>/CD34<sup>+</sup>/CD24<sup>+</sup> relative to DLK1<sup>−</sup>/CD34<sup>+</sup>/CD24<sup>−</sup> subpopulations.https://www.mdpi.com/2073-4409/10/2/214ex vivohuman adipose stem/progenitor cellsquiescencesenescencestemnessproliferation |
| spellingShingle | Florian M. Hatzmann Asim Ejaz G. Jan Wiegers Markus Mandl Camille Brucker Stefan Lechner Tina Rauchenwald Marit Zwierzina Saphira Baumgarten Sonja Wagner Monika Mattesich Petra Waldegger Gerhard Pierer Werner Zwerschke Quiescence, Stemness and Adipogenic Differentiation Capacity in Human DLK1<sup>−</sup>/CD34<sup>+</sup>/CD24<sup>+</sup> Adipose Stem/Progenitor Cells Cells ex vivo human adipose stem/progenitor cells quiescence senescence stemness proliferation |
| title | Quiescence, Stemness and Adipogenic Differentiation Capacity in Human DLK1<sup>−</sup>/CD34<sup>+</sup>/CD24<sup>+</sup> Adipose Stem/Progenitor Cells |
| title_full | Quiescence, Stemness and Adipogenic Differentiation Capacity in Human DLK1<sup>−</sup>/CD34<sup>+</sup>/CD24<sup>+</sup> Adipose Stem/Progenitor Cells |
| title_fullStr | Quiescence, Stemness and Adipogenic Differentiation Capacity in Human DLK1<sup>−</sup>/CD34<sup>+</sup>/CD24<sup>+</sup> Adipose Stem/Progenitor Cells |
| title_full_unstemmed | Quiescence, Stemness and Adipogenic Differentiation Capacity in Human DLK1<sup>−</sup>/CD34<sup>+</sup>/CD24<sup>+</sup> Adipose Stem/Progenitor Cells |
| title_short | Quiescence, Stemness and Adipogenic Differentiation Capacity in Human DLK1<sup>−</sup>/CD34<sup>+</sup>/CD24<sup>+</sup> Adipose Stem/Progenitor Cells |
| title_sort | quiescence stemness and adipogenic differentiation capacity in human dlk1 sup sup cd34 sup sup cd24 sup sup adipose stem progenitor cells |
| topic | ex vivo human adipose stem/progenitor cells quiescence senescence stemness proliferation |
| url | https://www.mdpi.com/2073-4409/10/2/214 |
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