Hatzmann, Florian M. and Ejaz, Asim and Wiegers, G. Jan and Mandl, Markus and Brucker, Camille and Lechner, Stefan and Rauchenwald, Tina and Zwierzina, Marit and Baumgarten, Saphira and Wagner, Sonja and Mattesich, Monika and Waldegger, Petra and Pierer, Gerhard and Zwerschke, Werner
(2021)
Quiescence, Stemness and Adipogenic Differentiation Capacity in Human DLK1−/CD34+/CD24+ Adipose Stem/Progenitor Cells.
Cells, 10 (2).
p. 214.
ISSN 2073-4409
Abstract
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+/CD34−, DLK1+/CD34dim and DLK1−/CD34+ cells. We demonstrate that DLK1−/CD34+ cells, the only population exhibiting proliferative and adipogenic capacity, express ex vivo the bonafide quiescence markers p21Cip1, p27Kip1 and p57Kip2 but neither proliferation markers nor the senescence marker p16Ink4a. 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−/CD34+/CD24− and DLK1−/CD34+/CD24+ fractions shows that KLF4 and c-MYC are higher expressed in DLK1−/CD34+/CD24+ 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−/CD34+/CD24+. Intriguingly, CD24 knock-down in these cells reduces proliferation and adipogenesis. In conclusion, DLK1−/CD34+ 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−/CD34+/CD24+ relative to DLK1−/CD34+/CD24− subpopulations.
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| Item Type: |
Article
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| Status: |
Published |
| Creators/Authors: |
| Creators | Email | Pitt Username | ORCID  |
|---|
| Hatzmann, Florian M. | | | | | Ejaz, Asim | asa118@pitt.edu | asa118 | | | Wiegers, G. Jan | | | | | Mandl, Markus | | | | | Brucker, Camille | | | | | Lechner, Stefan | | | | | Rauchenwald, Tina | | | | | Zwierzina, Marit | | | | | Baumgarten, Saphira | | | | | Wagner, Sonja | | | | | Mattesich, Monika | | | | | Waldegger, Petra | | | | | Pierer, Gerhard | | | | | Zwerschke, Werner | | | |
|
| Date: |
22 January 2021 |
| Date Type: |
Publication |
| Journal or Publication Title: |
Cells |
| Volume: |
10 |
| Number: |
2 |
| Publisher: |
MDPI AG |
| Page Range: |
p. 214 |
| DOI or Unique Handle: |
10.3390/cells10020214 |
| Schools and Programs: |
School of Medicine > Surgery |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
ex vivo, human adipose stem/progenitor cells, quiescence, senescence, stemness, proliferation |
| ISSN: |
2073-4409 |
| Official URL: |
http://dx.doi.org/10.3390/cells10020214 |
| Funders: |
European Union’s Horizon 2020, EUREGIO Environment Food and Health project funded by the European Region Tyrol-South-Tyrol-Trentino, University of Innsbruck, Förderungsbeiträge Aktion D. Swarovski KG 2017 |
| Article Type: |
Research Article |
| Date Deposited: |
28 Jun 2021 19:10 |
| Last Modified: |
28 Jun 2021 19:10 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/41354 |
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