NANOG Plays a Hierarchical Role in the Transcription Network Regulating the Pluripotency and Plasticity of Adipose Tissue-Derived Stem Cells
by
Maria Pitrone 1, Giuseppe Pizzolanti 1,*, Laura Tomasello 1, Antonina Coppola 1, Lorenzo Morini 2, Gianni Pantuso 2, Romina Ficarella 3, Valentina Guarnotta 1, Sebastio Perrini 3, Francesco Giorgino 3 and Carla Giordano 1,4,*
Maria Pitrone 1, Giuseppe Pizzolanti 1,*, Laura Tomasello 1, Antonina Coppola 1, Lorenzo Morini 2, Gianni Pantuso 2, Romina Ficarella 3, Valentina Guarnotta 1, Sebastio Perrini 3, Francesco Giorgino 3 and Carla Giordano 1,4,*
1
Aldo Galluzzo Laboratory of Regenerative Medicine, Section of Endocrinology, Diabetology and Metabolism, Di.Bi.M.I.S, University of Palermo, 90127 Palermo, Italy
2
Oncology Surgery, University of Palermo, 90127 Palermo, Italy
3
Endocrinology and Metabolic Diseases, University of Bari, 70124 Bari, Italy
4
ATeN (Advanced Technologies Network Center), University of Palermo, 90127 Palermo, Italy
*
Authors to whom correspondence should be addressed.
Academic Editor: Gehua Zhen
Int. J. Mol. Sci. 2017, 18(6), 1107; https://doi.org/10.3390/ijms18061107
Received: 18 January 2017 / Revised: 12 May 2017 / Accepted: 17 May 2017 / Published: 23 May 2017
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
The stromal vascular cell fraction (SVF) of visceral and subcutaneous adipose tissue (VAT and SAT) has increasingly come into focus in stem cell research, since these compartments represent a rich source of multipotent adipose-derived stem cells (ASCs). ASCs exhibit a self-renewal potential and differentiation capacity. Our aim was to study the different expression of the embryonic stem cell markers NANOG (homeobox protein NANOG), SOX2 (SRY (sex determining region Y)-box 2) and OCT4 (octamer-binding transcription factor 4) and to evaluate if there exists a hierarchal role in this network in ASCs derived from both SAT and VAT. ASCs were isolated from SAT and VAT biopsies of 72 consenting patients (23 men, 47 women; age 45 ± 10; BMI between 25 ± 5 and 30 ± 5 range) undergoing elective open-abdominal surgery. Sphere-forming capability was evaluated by plating cells in low adhesion plastic. Stem cell markers CD90, CD105, CD29, CD31, CD45 and CD146 were analyzed by flow cytometry, and the stem cell transcription factors NANOG, SOX2 and OCT4 were detected by immunoblotting and real-time PCR. NANOG, SOX2 and OCT4 interplay was explored by gene silencing. ASCs from VAT and SAT confirmed their mesenchymal stem cell (MSC) phenotype expressing the specific MSC markers CD90, CD105, NANOG, SOX2 and OCT4. NANOG silencing induced a significant OCT4 (70 ± 0.05%) and SOX2 (75 ± 0.03%) downregulation, whereas SOX2 silencing did not affect NANOG gene expression. Adipose tissue is an important source of MSC, and siRNA experiments endorse a hierarchical role of NANOG in the complex transcription network that regulates pluripotency.
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Keywords:
adipose derived stem cell (ASC); regenerative medicine; embryonic stem cell marker network
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
MDPI and ACS Style
Pitrone, M.; Pizzolanti, G.; Tomasello, L.; Coppola, A.; Morini, L.; Pantuso, G.; Ficarella, R.; Guarnotta, V.; Perrini, S.; Giorgino, F.; Giordano, C. NANOG Plays a Hierarchical Role in the Transcription Network Regulating the Pluripotency and Plasticity of Adipose Tissue-Derived Stem Cells. Int. J. Mol. Sci. 2017, 18, 1107.
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