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Adipose Tissue Biology pp 1–16Cite as

Adipocyte Precursors: Developmental Origins, Self-Renewal, and Plasticity

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Abstract

The current epidemic of obesity and overweight has caused a surge of interest in the study of adipose tissue formation. Much progress has been made in defining the transcriptional networks controlling the terminal differentiation of preadipocytes into mature adipocytes. However, the early steps that direct mesenchymal stem cells down the adipocyte lineage remain largely unknown. Similarly, the study of the developmental origin of adipocytes during embryogenesis has been largely disregarded until now. This review summarizes the surprising findings that have recently emerged from in vivo lineage tracing studies, unraveling unsuspected developmental origins for white adipocytes. We will propose that the differential origin of adipocytes could also reflect functional differences and site-specific regulations of adipose tissue. This chapter also reports recent work that has led to the identification of discrete immature cell populations from which white adipocytes are derived in mice.

A pool of adipocyte progenitors remains present in adipose tissue during adult life. This pool is responsible for the renewal of adipocytes and the potential of this tissue to expand in response to chronic energy overload. However, factors controlling proliferation and differentiation of human adipocyte progenitors are largely unknown. We will present stem cells derived from human adipose tissue (human Multipotent Adipose tissue Derived Stem (hMADS) cells) for studying proliferation and differentiation of adipocyte progenitors and will show that fibroblast growth factor 2 and activin A are key regulators of human adipocyte precursor self-renewal. Finally, we will discuss about the plasticity of hMADS cells.

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References

  • Bezaire V, Mairal A, Ribet C, Lefort C, Girousse A, Jocken J, Laurencikiene J, Anesia R, Rodriguez A-M, Ryden M, Stenson BM, Dani C, Ailhaud G, Arner P, Langin D (2009) Contribution of adipose triglyceride lipase and hormone-sensitive lipase to lypolysis in human hMADS adipocytes. J Biol Chem 284(27):18282–18291

    Article  PubMed  CAS  Google Scholar 

  • Billon N, Iannarelli P, Monteiro MC, Glavieux-Pardanaud C, Richardson WD, Kessaris N, Dani C, Dupin E (2007) The generation of adipocytes by the neural crest. Development 134:2283–2292

    Article  PubMed  CAS  Google Scholar 

  • Billon N, Monteiro MC, Dani C (2008) Developmental origin of adipocytes: new insights into a pending question. Biol Cell 100:563–575

    Article  PubMed  CAS  Google Scholar 

  • Billon N, Kolde R, Reimand J, Monteiro MC, Kull M, Peterson H, Tretyakov K, Adler P, Wdziekonski B, Vilo J, Dani C (2010) Comprehensive transcriptome analysis of mouse embryonic stem cell adipogenesis unravels new processes of adipocyte development. Genome Biol 11:R80

    Article  PubMed  Google Scholar 

  • Bourlier V, Zakaroff-Girard A, Miranville A, De Barros S, Maumus M, Sengenes C, Galitzky J, Lafontan M, Karpe F, Frayn KN, Bouloumie A (2008) Remodeling phenotype of human subcutaneous adipose tissue macrophages. Circulation 117:806–815

    Article  PubMed  CAS  Google Scholar 

  • Cancello R, Henegar C, Viguerie N, Taleb S, Poitou C, Rouault C, Coupaye M, Pelloux V, Hugol D, Bouillot JL, Bouloumie A, Barbatelli G, Cinti S, Svensson PA, Barsh GS, Zucker JD, Basdevant A, Langin D, Clement K (2005) Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss. Diabetes 54:2277–2286

    Article  PubMed  CAS  Google Scholar 

  • Carnevalli LS, Masuda K, Frigerio F, Le Bacquer O, Um SH, Gandin V, Topisirovic I, Sonenberg N, Thomas G, Kozma SC (2010) S6K1 plays a critical role in early adipocyte differentiation. Dev Cell 18:763–774

    Article  PubMed  CAS  Google Scholar 

  • Cousin B, Munoz O, Andre M, Fontanilles AM, Dani C, Cousin JL, Laharrague P, Casteilla L, Penicaud L (1999) A role for preadipocytes as macrophage-like cells. FASEB J 13:305–312

    PubMed  CAS  Google Scholar 

  • Crossno JT Jr, Majka SM, Grazia T, Gill RG, Klemm DJ (2006) Rosiglitazone promotes development of a novel adipocyte population from bone marrow-derived circulating progenitor cells. J Clin Invest 116:3220–3228

    Article  PubMed  CAS  Google Scholar 

  • Dani C, Smith A, Dessolin S, Leroy P, Staccini L, Villageois P, Darimont C, Ailhaud G (1997) Differentiation of embryonic stem cells into adipocytes in vitro. J Cell Sci 110:1279–1285

    PubMed  CAS  Google Scholar 

  • Dupin E, Creuzet S, Le Douarin NM (2006) The contribution of the neural crest to the vertebrate body. Adv Exp Med Biol 589:96–119

    Article  PubMed  CAS  Google Scholar 

  • Elabd C, Chiellini C, Massoudi A, Cochet O, Zaragosi LE, Trojani C, Michiels JF, Weiss P, Carle G, Rochet N, Dechesne CA, Ailhaud G, Dani C, Amri EZ (2007) Human adipose tissue-derived multipotent stem cells differentiate in vitro and in vivo into osteocyte-like cells. Biochem Biophys Res Commun 361:342–348

    Article  PubMed  CAS  Google Scholar 

  • Elabd C, Chiellini C, Carmona M, Galitzky J, Cochet O, Petersen R, Penicaud L, Kristiansen K, Bouloumie A, Casteilla L, Dani C, Ailhaud G, Amri EZ (2009) Human multipotent adipose-derived stem cells differentiate into functional brown adipocytes. Stem Cells 27:2753–2760

    Article  PubMed  CAS  Google Scholar 

  • Fontaine C, Cousin W, Plaisant M, Dani C, Peraldi P (2008) Hedgehog signaling alters adipocyte maturation of human mesenchymal stem cells. Stem Cells 26:1037–1046

    Article  PubMed  CAS  Google Scholar 

  • Gesta S, Bluher M, Yamamoto Y, Norris AW, Berndt J, Kralisch S, Boucher J, Lewis C, Kahn CR (2006) Evidence for a role of developmental genes in the origin of obesity and body fat distribution. Proc Natl Acad Sci USA 103:6676–6681

    Article  PubMed  CAS  Google Scholar 

  • Goodpaster BH, Wolf D (2004) Skeletal muscle lipid accumulation in obesity, insulin resistance, and type 2 diabetes. Pediatr Diabetes 5:219–226

    Article  PubMed  Google Scholar 

  • Goudenege S, Pisani DF, Wdziekonski B, Di Santo JP, Bagnis C, Dani C, Dechesne CA (2009) Enhancement of myogenic and muscle repair capacities of human adipose-derived stem cells with forced expression of MyoD. Mol Ther 17:1064–1072

    Article  PubMed  CAS  Google Scholar 

  • Hauner H, Entenmann G, Wabitsch M, Gaillard D, Ailhaud G, Negrel R, Pfeiffer EF (1989) Promoting effect of glucocorticoids on the differentiation of human adipocyte precursor cells cultured in a chemically defined medium. J Clin Invest 84:1663–1670

    Article  PubMed  CAS  Google Scholar 

  • Isakson P, Hammarstedt A, Gustafson B, Smith U (2009) Impaired preadipocyte differentiation in human abdominal obesity: role of Wnt, tumor necrosis factor-alpha, and inflammation. Diabetes 58:1550–1557

    Article  PubMed  CAS  Google Scholar 

  • Joe AW, Yi L, Natarajan A, Le Grand F, So L, Wang J, Rudnicki MA, Rossi FM (2010) Muscle injury activates resident fibro/adipogenic progenitors that facilitate myogenesis. Nat Cell Biol 12:153–163

    Article  PubMed  CAS  Google Scholar 

  • Kawaguchi J, Mee PJ, Smith AG (2005) Osteogenic and chondrogenic differentiation of embryonic stem cells in response to specific growth factors. Bone 36:758–769

    Article  PubMed  CAS  Google Scholar 

  • Keller GM (1995) In vitro differentiation of embryonic stem cells. Curr Opin Cell Biol 7:862–869

    Article  PubMed  CAS  Google Scholar 

  • Keophiphath M, Achard V, Henegar C, Rouault C, Clement K, Lacasa D (2009) Macrophage-secreted factors promote a profibrotic phenotype in human preadipocytes. Mol Endocrinol 23:11–24

    Article  PubMed  CAS  Google Scholar 

  • Lacasa D, Taleb S, Keophiphath M, Miranville A, Clement K (2007) Macrophage-secreted factors impair human adipogenesis: involvement of proinflammatory state in preadipocytes. Endocrinology 148:868–877

    Article  PubMed  CAS  Google Scholar 

  • Lafontan M, Sengenes C, Galitzky J, Berlan M, De Glisezinski I, Crampes F, Stich V, Langin D, Barbe P, Riviere D (2000) Recent developments on lipolysis regulation in humans and discovery of a new lipolytic pathway. Int J Obes Relat Metab Disord 24(Suppl 4):S47–S52

    PubMed  CAS  Google Scholar 

  • Li N, Kelsh RN, Croucher P, Roehl HH (2010) Regulation of neural crest cell fate by the retinoic acid and Pparg signalling pathways. Development 137:389–394

    Article  PubMed  CAS  Google Scholar 

  • Longo KA, Wright WS, Kang S, Gerin I, Chiang SH, Lucas PC, Opp MR, MacDougald OA (2004) Wnt10b inhibits development of white and brown adipose tissues. J Biol Chem 279:35503–35509

    Article  PubMed  CAS  Google Scholar 

  • Majka SM, Fox KE, Psilas JC, Helm KM, Childs CR, Acosta AS, Janssen RC, Friedman JE, Woessner BT, Shade TR, Varella-Garcia M, De KDJ (2010) novo generation of white adipocytes from the myeloid lineage via mesenchymal intermediates is age, adipose depot, and gender specific. Proc Natl Acad Sci USA 107:14781–14786

    Article  PubMed  CAS  Google Scholar 

  • Maumus M, Sengenes C, Decaunes P, Zakaroff-Girard A, Bourlier V, Lafontan M, Galitzky J, Bouloumie A (2008) Evidence of in situ proliferation of adult adipose tissue-derived progenitor cells: influence of fat mass microenvironment and growth. J Clin Endocrinol Metab 93:4098–4106

    Article  PubMed  CAS  Google Scholar 

  • Mohan A, Asselin J, Sargent IL, Groome NP, Muttukrishna S (2001) Effect of cytokines and growth factors on the secretion of inhibin A, activin A and follistatin by term placental villous trophoblasts in culture. Eur J Endocrinol 145:505–511

    Article  PubMed  CAS  Google Scholar 

  • Montague CT, Prins JB, Sanders L, Zhang J, Sewter CP, Digby J, Byrne CD, O’Rahilly S (1998) Depot-related gene expression in human subcutaneous and omental adipocytes. Diabetes 47:1384–1391

    Article  PubMed  CAS  Google Scholar 

  • Permana PA, Nair S, Lee YH, Luczy-Bachman G, Vozarova De Courten B, Tataranni PA (2004) Subcutaneous abdominal preadipocyte differentiation in vitro inversely correlates with central obesity. Am J Physiol Endocrinol Metab 286:E958–E962

    Article  PubMed  CAS  Google Scholar 

  • Pisani DF, Dechesne CA, Sacconi S, Delplace S, Belmonte N, Cochet O, Clement N, Wdziekonski B, Villageois AP, Butori C, Bagnis C, Di Santo JP, Kurzenne JY, Desnuelle C, Dani C (2010) Isolation of a highly myogenic CD34-negative subset of human skeletal muscle cells free of adipogenic potential. Stem Cells 28:753–764

    Article  PubMed  CAS  Google Scholar 

  • Poitou C, Divoux A, Faty A, Tordjman J, Hugol D, Aissat A, Keophiphath M, Henegar C, Commans S, Clement K (2009) Role of serum amyloid a in adipocyte-macrophage cross talk and adipocyte cholesterol efflux. J Clin Endocrinol Metab 94:1810–1817

    Article  PubMed  CAS  Google Scholar 

  • Rodeheffer MS, Birsoy K, Friedman JM (2008) Identification of white adipocyte progenitor cells in vivo. Cell 135:240–249

    Article  PubMed  CAS  Google Scholar 

  • Rodriguez A-M, Elabd C, Delteil F, Astier J, Vernochet C, Saint-Marc P, Guesnet J, Guezennec A, Amri E-Z, Dani C, Ailhaud G (2004) Adipocyte differentiation of multipotent cells established from human adipose tissue. Biochem Biophys Res Commun 315:255–263

    Article  PubMed  CAS  Google Scholar 

  • Rodriguez A-M, Pisani D, Dechesne CA, Turc-Carel C, Kurzenne J-Y, Wdziekonski B, Villageois A, Bagnis C, Breittmayer J-P, Groux H, Ailhaud G, Dani C (2005a) Transplantation of a multipotent cell population from human adipose tissue induces dystrophin expression in the immunocompetent mdx mouse. J Exp Med 201:1397–1405

    Article  PubMed  CAS  Google Scholar 

  • Rodriguez AM, Elabd C, Amri EZ, Ailhaud G, Dani C (2005b) The human adipose tissue is a source of multipotent stem cells. Biochimie 87:125–128

    Article  PubMed  CAS  Google Scholar 

  • Rosen ED, MacDougald OA (2006) Adipocyte differentiation from the inside out. Nat Rev Mol Cell Biol 7:885–896

    Article  PubMed  CAS  Google Scholar 

  • Rosen ED, Spiegelman BM (2000) Molecular regulation of adipogenesis. Annu Rev Cell Dev Biol 16:145–171

    Article  PubMed  CAS  Google Scholar 

  • Schulz TJ, Tseng YH (2009) Emerging role of bone morphogenetic proteins in adipogenesis and energy metabolism. Cytokine Growth Factor Rev 20:523–531

    Article  PubMed  CAS  Google Scholar 

  • Schulz H, Kolde R, Adler P, Aksoy I, Anastassiadis K, Bader M, Billon N, Boeuf H, Bourillot PY, Buchholz F, Dani C, Doss MX, Forrester L, Gitton M, Henrique D, Hescheler J, Himmelbauer H, Hubner N, Karantzali E, Kretsovali A, Lubitz S, Pradier L, Rai M, Reimand J, Rolletschek A, Sachinidis A, Savatier P, Stewart F, Storm MP, Trouillas M, Vilo J, Welham MJ, Winkler J, Wobus AM, Hatzopoulos AK (2009) The FunGenES database: a genomics resource for mouse embryonic stem cell differentiation. PLoS One 4:e6804

    Article  PubMed  Google Scholar 

  • Seale P, Kajimura S, Spiegelman BM (2009) Transcriptional control of brown adipocyte development and physiological function – of mice and men. Genes Dev 23:788–797

    Article  PubMed  CAS  Google Scholar 

  • Sengenes C, Lolmede K, Zakaroff-Girard A, Busse R, Bouloumie A (2005) Preadipocytes in the human subcutaneous adipose tissue display distinct features from the adult mesenchymal and hematopoietic stem cells. J Cell Physiol 205:114–122

    Article  PubMed  CAS  Google Scholar 

  • Sera Y, LaRue AC, Moussa O, Mehrotra M, Duncan JD, Williams CR, Nishimoto E, Schulte BA, Watson PM, Watson DK, Ogawa M (2009) Hematopoietic stem cell origin of adipocytes. Exp Hematol 37:1108–1120, e1101–1104

    Google Scholar 

  • Sethi JK, Vidal-Puig AJ (2007) Thematic review series: adipocyte biology. Adipose tissue function and plasticity orchestrate nutritional adaptation. J Lipid Res 48:1253–1262

    Article  PubMed  CAS  Google Scholar 

  • Smith AG (1992) Mouse embryo stem cells: their identification, propagation and manipulation. Semin Cell Biol 3:385–399

    Article  PubMed  CAS  Google Scholar 

  • Spalding KL, Arner E, Westermark PO, Bernard S, Buchholz BA, Bergmann O, Blomqvist L, Hoffstedt J, Naslund E, Britton T, Concha H, Hassan M, Ryden M, Frisen J, Arner P (2008) Dynamics of fat cell turnover in humans. Nature 453:783–787

    Article  PubMed  CAS  Google Scholar 

  • Takashima Y, Era T, Nakao K, Kondo S, Kasuga M, Smith AG, Nishikawa S (2007) Neuroepithelial cells supply an initial transient wave of MSC differentiation. Cell 129:1377–1388

    Article  PubMed  CAS  Google Scholar 

  • Tang W, Zeve D, Suh JM, Bosnakovski D, Kyba M, Hammer RE, Tallquist MD, Graff JM (2008) White fat progenitor cells reside in the adipose vasculature. Science 322:583–586

    Article  PubMed  CAS  Google Scholar 

  • Taura D, Noguchi M, Sone M, Hosoda K, Mori E, Okada Y, Takahashi K, Homma K, Oyamada N, Inuzuka M, Sonoyama T, Ebihara K, Tamura N, Itoh H, Suemori H, Nakatsuji N, Okano H, Yamanaka S, Nakao K (2009) Adipogenic differentiation of human induced pluripotent stem cells: comparison with that of human embryonic stem cells. FEBS Lett 583:1029–1033

    Article  PubMed  CAS  Google Scholar 

  • Tchkonia T, Lenburg M, Thomou T, Giorgadze N, Frampton G, Pirtskhalava T, Cartwright A, Cartwright M, Flanagan J, Karagiannides I, Gerry N, Forse RA, Tchoukalova Y, Jensen MD, Pothoulakis C, Kirkland JL (2007) Identification of depot-specific human fat cell progenitors through distinct expression profiles and developmental gene patterns. Am J Physiol Endocrinol Metab 292:E298–E307

    Article  PubMed  CAS  Google Scholar 

  • Timmons JA, Wennmalm K, Larsson O, Walden TB, Lassmann T, Petrovic N, Hamilton DL, Gimeno RE, Wahlestedt C, Baar K, Nedergaard J, Cannon B (2007) Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages. Proc Natl Acad Sci USA 104:4401–4406

    Article  PubMed  CAS  Google Scholar 

  • Tong Q, Dalgin G, Xu H, Ting CN, Leiden JM, Hotamisligil GS (2000) Function of GATA transcription factors in preadipocyte-adipocyte transition. Science 290:134–138

    Article  PubMed  CAS  Google Scholar 

  • Uezumi A, Fukada S, Yamamoto N, Takeda S, Tsuchida K (2010) Mesenchymal progenitors distinct from satellite cells contribute to ectopic fat cell formation in skeletal muscle. Nat Cell Biol 12:143–152

    Article  PubMed  CAS  Google Scholar 

  • Wdziekonski B, Villageois P, Dani C (2003) Development of adipocytes from differentiated ES cells. Methods Enzymol 365:268–277

    Article  PubMed  CAS  Google Scholar 

  • Wdziekonski B, Villageois P, Vernochet C, Phillips B, Dani C (2006) Use of differentiating embryonic stem cells in pharmacological studies. Methods Mol Biol 329:341–351

    PubMed  CAS  Google Scholar 

  • Wdziekonski B, Villageois P, Dani C (2007) Differentiation of mouse embryonic stem cells and of human adult stem cells into adipocytes. Curr Protoc Cell Biol Chapter 23:Unit 23.4

    Google Scholar 

  • Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112:1796–1808

    PubMed  CAS  Google Scholar 

  • Widberg CH, Newell FS, Bachmann AW, Ramnoruth SN, Spelta MC, Whitehead JP, Hutley LJ, Prins JB (2009) Fibroblast growth factor receptor 1 is a key regulator of early adipogenic events in human preadipocytes. Am J Physiol Endocrinol Metab 296:E121–E131

    Article  PubMed  CAS  Google Scholar 

  • Wren TA, Bluml S, Tseng-Ong L, Gilsanz V (2008) Three-point technique of fat quantification of muscle tissue as a marker of disease progression in Duchenne muscular dystrophy: preliminary study. AJR Am J Roentgenol 190:W8–W12

    Article  PubMed  Google Scholar 

  • Xiong C, Xie CQ, Zhang L, Zhang J, Xu K, Fu M, Thompson WE, Yang LJ, Chen YE (2005) Derivation of adipocytes from human embryonic stem cells. Stem Cells Dev 14:671–675

    Article  PubMed  CAS  Google Scholar 

  • Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112:1821–1830

    PubMed  CAS  Google Scholar 

  • Zaragosi LE, Ailhaud G, Dani C (2006) Autocrine fibroblast growth factor 2 signaling is critical for self-renewal of human multipotent adipose-derived stem cells. Stem Cells 24:2412–2419

    Article  PubMed  CAS  Google Scholar 

  • Zaragosi LE, Wdziekonski B, Villageois P, Keophiphath M, Maumus M, Tchkonia T, Bourlier V, Mohsen-Kanson T, Ladoux A, Elabd C, Scheideler M, Trajanoski Z, Takashima Y, Amri EZ, Lacasa D, Sengenes C, Ailhaud G, Clement K, Bouloumie A, Kirkland JL, Dani C (2010) Activin A plays a critical role in proliferation and differentiation of human adipose progenitors. Diabetes 59(10):2513–2521

    Article  PubMed  CAS  Google Scholar 

  • Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhaim P, Lorenz HP, Hedrick MH (2001) Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng 7:211–228

    Article  PubMed  CAS  Google Scholar 

  • Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P, Hedrick MH (2002) Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 13:4279–4295

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Institute of Developmental Biology and Cancer, University of Nice Sophia-Antipolis, UMR6543 Centre National de la Recherche Scientifique (CNRS), 06107, Nice, Cedex 2, France

    Christian Dani & Nathalie Billon

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  1. Christian Dani
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  2. Nathalie Billon
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Correspondence to Christian Dani .

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  1. Queen's Medical Centre, School of Human Development, University Hospital, Nottingham, NG7 2UH, United Kingdom

    Michael E. Symonds

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Dani, C., Billon, N. (2012). Adipocyte Precursors: Developmental Origins, Self-Renewal, and Plasticity. In: Symonds, M. (eds) Adipose Tissue Biology. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-0965-6_1

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