Epigenetic programming of mesenchymal stem cells from human adipose tissue

Boquest, Andrew C.; Noer, Agate; Collas, Philippe

doi:10.1007/bf02698059

Cited by 78 publications

(62 citation statements)

References 101 publications

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“…analyses of gene expression ( 108,110,111 ) and protein secretion ( 112 ), and by more-focused approaches, such as assessment of epigenetics ( 113 ), circadian genes ( 114 ), or electrophysiological properties ( 115 ). However, by far the most widespread analyses are of cell surface markers.…”

Section: Defining the Ascmentioning

confidence: 99%

Adipose tissue stem cells meet preadipocyte commitment: going back to the future

Cawthorn

Scheller

MacDougald

2012

Journal of Lipid Research

356

323

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with ill health. Such stigmatization distracts from a fascinating aspect of WAT biology: its enormous plasticity as an organ. Indeed, WAT is capable of massive expansion and contraction in response to chronic alterations in energy balance, accounting for as little as 5% body mass in extremely lean athletes ( 1 ) or as much as 60% body mass in morbidly obese individuals ( 2 ). Moreover in rodents, rabbits, and humans, WAT can regenerate following lipectomy ( 3-6 ). This striking degree of plasticity is unique among organs in adults. On a cellular level, WAT expansion is driven by both hypertrophy and hyperplasia of adipocytes ( 7-13 ). Even in nonexpanding WAT, adipocytes renew frequently to compensate for adipocyte death, with approximately 10% of adipocytes renewed annually ( 14,15 ). These data, which indicate that committed adipocyte progenitors (preadipocytes) exist within WAT, are the product of decades of research motivated largely by our desire to understand adipose tissue in the context of obesity and related diseases. Preadipocytes exist in adipose tissueThough the notion of obesity as a disease has existed since at least the time of Hippocrates ( 16 ), investigation into the origins of the adipocyte and the individual contributions of adipocyte hypertrophy and hyperplasia to adipose bulk began in earnest only after the appearance of the stem cell concept, as related to blood cells, in the early 1900s ( 17 ). In the 1940s, histologic observations of the appearance of adipocytes in chambers implanted in the ears of live rabbits suggested that de novo fat formation was Abstract White adipose tissue (WAT) is perhaps the most plastic organ in the body, capable of regeneration following surgical removal and massive expansion or contraction in response to altered energy balance. Research conducted for over 70 years has investigated adipose tissue plasticity on a cellular level, spurred on by the increasing burden that obesity and associated diseases are placing on public health globally. This work has identifi ed committed preadipocytes in the stromal vascular fraction of adipose tissue and led to our current understanding that adipogenesis is important not only for WAT expansion, but also for maintenance of adipocyte numbers under normal metabolic states. At the turn of the millenium, studies investigating preadipocyte differentiation collided with developments in stem cell research, leading to the discovery of multipotent stem cells within WAT. Such adipose tissue-derived stem cells (ASCs) are capable of differentiating into numerous cell types of both mesodermal and nonmesodermal origin, leading to their extensive investigation from a therapeutic and tissue engineering perspective. However, the insights gained through studying ASCs have also contributed to more-recent progress in attempts to better characterize committed preadipocytes in adipose tissue. Thus, ASC research has gone back to its roots, thereby expanding our knowledge of preadipocyte commitment and adipose tissue biology. -Cawthorn, W. P., E. ...

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Section: Defining the Ascmentioning

confidence: 99%

Adipose tissue stem cells meet preadipocyte commitment: going back to the future

Cawthorn

Scheller

MacDougald

2012

Journal of Lipid Research

356

323

View full text Add to dashboard Cite

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“…This in turn is modulated by chromatin remodeling factors, which modify the balance between euchromatin and heterochromatin. These particular factors are also known to be involved in determining self-renewal, proliferation and differentiation potential of stem cells (Boquest et al, 2006;Squillaro et al, 2008). Chromatin remodelers such as the ATP-dependent remodeling complexes which contain Brg1 are required for cell cycle control, apoptosis and cell differentiation.…”

Section: In Vitro Senescence and Epigeneticsmentioning

confidence: 99%

Controversial issue: Is it safe to employ mesenchymal stem cells in cell-based therapies?

Lepperdinger

Brunauer

Jamnig

et al. 2008

Experimental Gerontology

113

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“…Human mesenchymal stem cells (MSCs) have been shown to differentiate not only into mesenchymal lineages (such as osteogenic, chondrogenic, adipogenic, and myogenic), but also into neurogenic, angiogenic, and hepatic lineages (Zuk et al, 2002;Baksh et al, 2004;Boquest et al, 2006a;Schaffler and Buchler, 2007). The pluripotent nature of MSCs makes them potentially ideal candidates for tissue engineering, and they have already demonstrated some efficacy in cell therapy and regenerative medicine Kassem, 2004;Leo and Grande, 2006;Mimeault and Batra, 2006).…”

Section: Introductionmentioning

confidence: 99%

“…The pluripotent nature of MSCs makes them potentially ideal candidates for tissue engineering, and they have already demonstrated some efficacy in cell therapy and regenerative medicine Kassem, 2004;Leo and Grande, 2006;Mimeault and Batra, 2006). Adipose tissue contains a supportive stroma that can be easily isolated and provides a rich source of MSCs (Zuk et al, 2002;Boquest et al, 2006a). Thus, adipose tissue represents a valuable source of multilineage stem cells.…”

mentioning

confidence: 99%

cAMP-mediated Induction of Cyclin E Sensitizes Growth-arrested Adipose Stem Cells to DNA Damage–induced Apoptosis

Ugland

Boquest

Naderi

et al. 2008

MBoC

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The differentiation capacity of mesenchymal stem cells has been extensively studied, but little is known on cell cycle-related events in the proliferation and differentiation phases of these cells. Here, we demonstrate that exposure to cAMP-increasing agents inhibits proliferation of adipose stem cells (ASCs). This antiproliferative effect is associated with both reduced cdk2 activity and pRB phosphorylation. Concomitantly, however, the level of cyclin E markedly increases upon cAMP induction, indicating that cyclin E may have cdk2-independent functions in these cells besides its role as a cdk2 activator. Indeed, we found indications of a cdk2-independent role of cyclin E in DNA damage-induced apoptosis. 8-CPT-cAMP sensitizes ASCs to ␥-irradiation-induced apoptosis, an effect abolished by knockdown of cyclin E. Moreover, cAMP induces early activation of ERK, leading to reduced degradation of cyclin E. The cAMP-mediated upregulation of cyclin E was blocked by knockdown of ERK or by an inhibitor of the ERK kinase MEK. We conclude that cAMP inhibits cdk2 activity and pRB phosphorylation, leading to reduced ASC proliferation. Concomitant with this growth inhibition, however, cyclin E levels are increased in a MEK/ERK-dependent manner. Our results suggest that cyclin E plays an important, cdk2-independent role in genotoxic stress-induced apoptosis in mesenchymal stem cells. INTRODUCTIONHuman mesenchymal stem cells (MSCs) have been shown to differentiate not only into mesenchymal lineages (such as osteogenic, chondrogenic, adipogenic, and myogenic), but also into neurogenic, angiogenic, and hepatic lineages (Zuk et al., 2002;Baksh et al., 2004;Boquest et al., 2006a;Schaffler and Buchler, 2007). The pluripotent nature of MSCs makes them potentially ideal candidates for tissue engineering, and they have already demonstrated some efficacy in cell therapy and regenerative medicine Kassem, 2004;Leo and Grande, 2006;Mimeault and Batra, 2006). Adipose tissue contains a supportive stroma that can be easily isolated and provides a rich source of MSCs (Zuk et al., 2002;Boquest et al., 2006a). Thus, adipose tissue represents a valuable source of multilineage stem cells. It is therefore important to understand the biology of adipose stem cells (ASCs).Cyclic AMP (cAMP) is a ubiquitous second messenger that regulates a number of different cellular processes, including metabolism, growth, differentiation, and gene regulation (Krebs and Beavo, 1979;McKnight, 1991;Vossler et al., 1997;Daniel et al., 1998;Kim et al., 2005). Most effects of cAMP are mediated through activation of protein kinase A (PKA) or the Epac (exchange protein directly activated by cAMP) family of exchange proteins (Walsh et al., 1968;Bos, 2003). Elevation of intracellular cAMP has both proliferative and antiproliferative effects depending on the cell type. For instance, cAMP stimulates the proliferation of thyroid cells, neurons, and Swiss 3T3 cells, while inhibiting the proliferation of lymphocytes, fibroblasts, and adipocytes (Rozengurt et al., 1981;Blomhoff et ...

show abstract

Epigenetic programming of mesenchymal stem cells from human adipose tissue

Cited by 78 publications

References 101 publications

Adipose tissue stem cells meet preadipocyte commitment: going back to the future

Adipose tissue stem cells meet preadipocyte commitment: going back to the future

Controversial issue: Is it safe to employ mesenchymal stem cells in cell-based therapies?

cAMP-mediated Induction of Cyclin E Sensitizes Growth-arrested Adipose Stem Cells to DNA Damage–induced Apoptosis

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