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Bayindir I, Babaeikelishomi R, Kocanova S, et al. Transcriptional Pathways in cPGI2-Induced Adipocyte Progenitor Activation for Browning. Front Endocrinol (Lausanne). 2015;6:129doi: 10.3389/fendo.2015.00129.
Bayindir, I., Babaeikelishomi, R., Kocanova, S., Sousa, I. S., Lerch, S., Hardt, O., Wild, S., Bosio, A., Bystricky, K., Herzig, S., & Vegiopoulos, A. (2015). Transcriptional Pathways in cPGI2-Induced Adipocyte Progenitor Activation for Browning. Frontiers in endocrinology, 6129. https://doi.org/10.3389/fendo.2015.00129
Bayindir, Irem, et al. "Transcriptional Pathways in cPGI2-Induced Adipocyte Progenitor Activation for Browning." Frontiers in endocrinology vol. 6 (2015): 129. doi: https://doi.org/10.3389/fendo.2015.00129
Bayindir I, Babaeikelishomi R, Kocanova S, Sousa IS, Lerch S, Hardt O, Wild S, Bosio A, Bystricky K, Herzig S, Vegiopoulos A. Transcriptional Pathways in cPGI2-Induced Adipocyte Progenitor Activation for Browning. Front Endocrinol (Lausanne). 2015 Aug 17;6:129. doi: 10.3389/fendo.2015.00129. eCollection 2015. PMID: 26347713; PMCID: PMC4538297.
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Front Endocrinol (Lausanne). 2015 Aug 17;6:129. doi: 10.3389/fendo.2015.00129. eCollection 2015.

Transcriptional Pathways in cPGI2-Induced Adipocyte Progenitor Activation for Browning.

Frontiers in endocrinology

Irem Bayindir, Rohollah Babaeikelishomi, Silvia Kocanova, Isabel Sofia Sousa, Sarah Lerch, Olaf Hardt, Stefan Wild, Andreas Bosio, Kerstin Bystricky, Stephan Herzig, Alexandros Vegiopoulos

Affiliations

  1. DKFZ Junior Group Metabolism and Stem Cell Plasticity, German Cancer Research Center , Heidelberg , Germany.
  2. University of Toulouse (UPS) , Toulouse , France ; Laboratoire de Biologie Moléculaire des Eucaryotes, Centre national de la recherche scientifique , Toulouse , France.
  3. DKFZ Junior Group Metabolism and Stem Cell Plasticity, German Cancer Research Center , Heidelberg , Germany ; Department of Life Sciences, University of Coimbra , Coimbra , Portugal.
  4. Miltenyi Biotec GmbH , Bergisch Gladbach , Germany.
  5. Helmholtz Center Munich, Institute for Diabetes and Cancer IDC , Neuherberg , Germany ; Joint Heidelberg-IDC Translational Diabetes Program, Heidelberg University Hospital , Heidelberg , Germany.

PMID: 26347713 PMCID: PMC4538297 DOI: 10.3389/fendo.2015.00129

Abstract

De novo formation of beige/brite adipocytes from progenitor cells contributes to the thermogenic adaptation of adipose tissue and holds great potential for the therapeutic remodeling of fat as a treatment for obesity. Despite the recent identification of several factors regulating browning of white fat, there is a lack of physiological cell models for the mechanistic investigation of progenitor-mediated beige/brite differentiation. We have previously revealed prostacyclin (PGI2) as one of the few known endogenous extracellular mediators promoting de novo beige/brite formation by relaying β-adrenergic stimulation to the progenitor level. Here, we present a cell model based on murine primary progenitor cells defined by markers previously shown to be relevant for in vivo browning, including a simplified isolation procedure. We demonstrate the specific and broad induction of thermogenic gene expression by PGI2 signaling in the absence of lineage conversion, and reveal the previously unidentified nuclear relocalization of the Ucp1 gene locus in association with transcriptional activation. By profiling the time course of the progenitor response, we show that PGI2 signaling promoted progenitor cell activation through cell cycle and adhesion pathways prior to metabolic maturation toward an oxidative cell phenotype. Our results highlight the importance of core progenitor activation pathways for the recruitment of thermogenic cells and provide a resource for further mechanistic investigation.

Keywords: PGI2; adipocyte cell model; adipocyte progenitors; adipose tissue remodeling; beige/brite differentiation; nuclear localization; prostacyclin

References

  1. Am J Physiol Endocrinol Metab. 2010 Jun;298(6):E1244-53 - PubMed
  2. Nat Med. 2013 Oct;19(10):1338-44 - PubMed
  3. Sci Transl Med. 2014 Jul 30;6(247):247ra103 - PubMed
  4. Cell. 2014 Jun 5;157(6):1292-308 - PubMed
  5. Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50 - PubMed
  6. Proc Natl Acad Sci U S A. 2011 Jan 4;108(1):143-8 - PubMed
  7. Cell Metab. 2014 Jul 1;20(1):103-18 - PubMed
  8. Biochem J. 1989 Jan 15;257(2):399-405 - PubMed
  9. FASEB J. 2015 Jan;29(1):286-99 - PubMed
  10. Bioinformatics. 2010 Mar 1;26(5):696-7 - PubMed
  11. Proc Natl Acad Sci U S A. 2007 Mar 13;104(11):4401-6 - PubMed
  12. J Clin Invest. 2015 Feb;125(2):478-86 - PubMed
  13. Curr Opin Genet Dev. 1998 Feb;8(1):28-35 - PubMed
  14. Cell. 2012 Jul 20;150(2):366-76 - PubMed
  15. Physiol Rev. 1999 Oct;79(4):1193-226 - PubMed
  16. Curr Opin Genet Dev. 2013 Apr;23(2):96-103 - PubMed
  17. Genes Dev. 1996 Apr 15;10(8):974-84 - PubMed
  18. Obesity (Silver Spring). 2009 May;17(5):965-72 - PubMed
  19. J Biol Chem. 2010 Mar 5;285(10 ):7153-64 - PubMed
  20. Biotechniques. 2003 Feb;34(2):374-8 - PubMed
  21. Nat Cell Biol. 2013 Jun;15(6):659-67 - PubMed
  22. Metabolism. 2014 Oct;63(10):1238-49 - PubMed
  23. Cell. 2015 Jan 15;160(1-2):105-18 - PubMed
  24. Science. 2010 May 28;328(5982):1158-61 - PubMed
  25. Cell Metab. 2012 Apr 4;15(4):480-91 - PubMed
  26. Cell Metab. 2013 Sep 3;18(3):355-67 - PubMed
  27. Proc Natl Acad Sci U S A. 2004 Mar 23;101(12 ):4112-7 - PubMed
  28. Cell. 2008 Oct 17;135(2):240-9 - PubMed
  29. Cell Metab. 2005 Nov;2(5):283-95 - PubMed
  30. J Cell Sci. 2000 May;113 ( Pt 9):1565-76 - PubMed
  31. Nat Cell Biol. 2013 Mar;15(3):302-8 - PubMed
  32. J Biol Chem. 1995 Jun 2;270(22):12953-6 - PubMed
  33. Am J Physiol Endocrinol Metab. 2012 Jan 1;302(1):E19-31 - PubMed
  34. Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):44-9 - PubMed
  35. PLoS One. 2010 Jun 30;5(6):e11391 - PubMed
  36. Nat Med. 2013 Oct;19(10 ):1252-63 - PubMed
  37. Eur J Biochem. 2003 Feb;270(4):699-705 - PubMed
  38. Science. 2014 Dec 5;346(6214):1238-42 - PubMed
  39. PLoS Genet. 2010 Apr 22;6(4):e1000922 - PubMed

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