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Open AccessArticle

Quiescence, Stemness and Adipogenic Differentiation Capacity in Human DLK1/CD34+/CD24+ Adipose Stem/Progenitor Cells

1
Division of Cell Metabolism and Differentiation Research, Research Institute for Biomedical Aging Research, University of Innsbruck, Rennweg 10, A-6020 Innsbruck, Austria
2
Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innrain 80-82, A-6020 Innsbruck, Austria
3
Department of Plastic Surgery, University of Pittsburgh Medical Center, 3550 Terrace Street, 6B Scaife Hall, Pittsburgh, PA 15261, USA
4
Division of Developmental Immunology, Biocenter, Medical University of Innsbruck, Innrain 80-82, A-6020 Innsbruck, Austria
5
Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Innsbruck, Anichstraße 35, A-6020 Innsbruck, Austria
*
Author to whom correspondence should be addressed.
Academic Editor: Bruce A. Bunnell
Cells 2021, 10(2), 214; https://doi.org/10.3390/cells10020214
Received: 23 November 2020 / Revised: 13 January 2021 / Accepted: 16 January 2021 / Published: 22 January 2021
(This article belongs to the Special Issue Research on Adipose Stem 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+/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. View Full-Text
Keywords: ex vivo; human adipose stem/progenitor cells; quiescence; senescence; stemness; proliferation; adipogenesis ex vivo; human adipose stem/progenitor cells; quiescence; senescence; stemness; proliferation; adipogenesis
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MDPI and ACS Style

Hatzmann, F.M.; Ejaz, A.; Wiegers, G.J.; Mandl, M.; Brucker, C.; Lechner, S.; Rauchenwald, T.; Zwierzina, M.; Baumgarten, S.; Wagner, S.; Mattesich, M.; Waldegger, P.; Pierer, G.; Zwerschke, W. Quiescence, Stemness and Adipogenic Differentiation Capacity in Human DLK1/CD34+/CD24+ Adipose Stem/Progenitor Cells. Cells 2021, 10, 214. https://doi.org/10.3390/cells10020214

AMA Style

Hatzmann FM, Ejaz A, Wiegers GJ, Mandl M, Brucker C, Lechner S, Rauchenwald T, Zwierzina M, Baumgarten S, Wagner S, Mattesich M, Waldegger P, Pierer G, Zwerschke W. Quiescence, Stemness and Adipogenic Differentiation Capacity in Human DLK1/CD34+/CD24+ Adipose Stem/Progenitor Cells. Cells. 2021; 10(2):214. https://doi.org/10.3390/cells10020214

Chicago/Turabian Style

Hatzmann, Florian M.; Ejaz, Asim; Wiegers, G. J.; Mandl, Markus; Brucker, Camille; Lechner, Stefan; Rauchenwald, Tina; Zwierzina, Marit; Baumgarten, Saphira; Wagner, Sonja; Mattesich, Monika; Waldegger, Petra; Pierer, Gerhard; Zwerschke, Werner. 2021. "Quiescence, Stemness and Adipogenic Differentiation Capacity in Human DLK1/CD34+/CD24+ Adipose Stem/Progenitor Cells" Cells 10, no. 2: 214. https://doi.org/10.3390/cells10020214

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