scholarly journals FTO intronic SNP strongly influences human neck adipocyte browning determined by tissue and PPARγ specific regulation: a transcriptome analysis

2020 ◽  
Author(s):  
Beáta B. Tóth ◽  
Rini Arianti ◽  
Abhirup Shaw ◽  
Attila Vámos ◽  
Zoltán Veréb ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Subcutaneous Fat ◽  
Obesity Risk ◽  
Differentiation Potential ◽  
Brown Adipocytes ◽  
White Adipocytes ◽  
Adipose Derived Stromal Cells ◽  
Extracellular Matrix Remodelling ◽  
Specific Regulation

AbstractBrown adipocytes, abundant in deep-neck (DN) area in humans, are thermogenic with anti-obesity potential. FTO pro-obesity rs1421085 T-to-C SNP shifts differentiation program towards white adipocytes in subcutaneous fat. Human adipose-derived stromal cells were obtained from subcutaneous neck (SC) and DN fat of 9 donors, of which 3-3 carried risk-free (T/T), heterozygous or obesity-risk (C/C) FTO genotypes. They were differentiated to white and brown (long-term PPARγ stimulation) adipocytes, then global RNA sequencing was performed and differentially expressed genes (DEGs) were compared. DN and SC progenitors had similar adipocyte differentiation potential but differed in DEGs. DN adipocytes displayed higher browning features according to ProFAT or BATLAS scores and characteristic DEG patterns revealing associated pathways which were highly expressed (thermogenesis, interferon, cytokine, retinoic acid, with UCP1 and BMP4 as prominent network stabilizers) or downregulated (particularly extracellular matrix remodelling) compared to SC ones. Part of DEGs in either DN or SC browning was PPARγ-dependent. Presence of the FTO obesity-risk allele suppressed the expression of mitochondrial and thermogenesis genes with a striking resemblance between affected pathways and those appearing in ProFAT and BATLAS, underlining the importance of metabolic and mitochondrial pathways in thermogenesis. Among overlapping regulatory influences which determine browning and thermogenic potential of neck adipocytes, FTO genetic background has a so far not recognized prominence.

scholarly journals FTO Intronic SNP Strongly Influences Human Neck Adipocyte Browning Determined by Tissue and PPARγ Specific Regulation: A Transcriptome Analysis

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 987 ◽  
Author(s):  
Beáta B. Tóth ◽  
Rini Arianti ◽  
Abhirup Shaw ◽  
Attila Vámos ◽  
Zoltán Veréb ◽  
...  
Keyword(s):  
Subcutaneous Fat ◽  
Peroxisome Proliferator ◽  
Matrix Remodeling ◽  
Obesity Risk ◽  
Differentiation Potential ◽  
Peroxisome Proliferator Activated Receptor ◽  
White Adipocytes ◽  
Adipose Derived Stromal Cells ◽  
Specific Regulation

Brown adipocytes, abundant in deep-neck (DN) area in humans, are thermogenic with anti-obesity potential. FTO pro-obesity rs1421085 T-to-C single-nucleotide polymorphism (SNP) shifts differentiation program towards white adipocytes in subcutaneous fat. Human adipose-derived stromal cells were obtained from subcutaneous neck (SC) and DN fat of nine donors, of which 3-3 carried risk-free (T/T), heterozygous or obesity-risk (C/C) FTO genotypes. They were differentiated to white and brown (long-term Peroxisome proliferator-activated receptor gamma (PPARγ) stimulation) adipocytes; then, global RNA sequencing was performed and differentially expressed genes (DEGs) were compared. DN and SC progenitors had similar adipocyte differentiation potential but differed in DEGs. DN adipocytes displayed higher browning features according to ProFAT or BATLAS scores and characteristic DEG patterns revealing associated pathways which were highly expressed (thermogenesis, interferon, cytokine, and retinoic acid, with UCP1 and BMP4 as prominent network stabilizers) or downregulated (particularly extracellular matrix remodeling) compared to SC ones. Part of DEGs in either DN or SC browning was PPARγ-dependent. Presence of the FTO obesity-risk allele suppressed the expression of mitochondrial and thermogenesis genes with a striking resemblance between affected pathways and those appearing in ProFAT and BATLAS, underlining the importance of metabolic and mitochondrial pathways in thermogenesis. Among overlapping regulatory influences that determine browning and thermogenic potential of neck adipocytes, FTO genetic background has a thus far not recognized prominence.

Adipose Tissue-Derived Stromal Cells Grown in Three-Dimensional Aliginate Constructs Display a Chondrogenic Phenotype

2000 ◽  
Author(s):  
Geoffrey R. Erickson ◽  
Jeffrey M. Gimble ◽  
Dawn Franklin ◽  
Farshid Guilak
Keyword(s):  
Articular Cartilage ◽  
Stromal Cells ◽  
Cartilage Damage ◽  
Donor Site ◽  
Subcutaneous Fat ◽  
Three Dimensional ◽  
Current Therapy ◽  
Chondrogenic Potential ◽  
Adipose Derived Stromal Cells ◽  
Chondrogenic Phenotype

Abstract Articular cartilage is the connective tissue that lines the surfaces of diarthrodial joints in the human body. Because cartilage is avascular, aneural, and alymphatic, it has a limited capacity for repair. Techniques such as microfracture, transplantation of autologous cartilage, and allograft or xenograft transplantations have not proven fully effective in treating cartilage damage. Current therapy is focusing on cell-based treatments such as autologous chondrocyte transplantation [1,2]. However, this method faces several limitations, as the donor site can provide a limited number of cells and the harvesting procedure itself may cause significant local morbidity. The goal of this study was to examine the chondrogenic potential of an autologous source of undifferentiated stromal cells derived from subcutaneous fat. It has been shown that chondrocytes embedded in a three-dimensional matrix retain a differentiated phenotype and produce cartilage-associated proteins [3]. In addition, it has been shown that alginate or agarose can support the formation of an extracellular matrix over time [4,5]. The goal of this study was to examine the chondrogenic potential of adipose-derived stromal cells with the ultimate goal of developing a “tissue engineering” method to regenerate articular cartilage.

scholarly journals Characterization of Human Knee and Chin Adipose-Derived Stromal Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Magali Kouidhi ◽  
Phi Villageois ◽  
Carine M. Mounier ◽  
Corinne Ménigot ◽  
Yves Rival ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Expression Profiles ◽  
Donor Site ◽  
Subcutaneous Fat ◽  
Gene Expression Profiles ◽  
Fat Grafting ◽  
Human Knee ◽  
Fat Depots ◽  
Adipose Derived Stromal Cells ◽  
Molecular Matching

Animal study findings have revealed that individual fat depots are not functionally equivalent and have different embryonic origins depending on the anatomic location. Mouse bone regeneration studies have also shown that it is essential to match theHoxcode of transplanted cells and host tissues to achieve correct repair. However, subcutaneous fat depots from any donor site are often used in autologous fat grafting. Our study was thus carried out to determine the embryonic origins of human facial (chin) and limb (knee) fat depots and whether they had similar features and molecular matching patterns. Paired chin and knee fat depots were harvested from 11 subjects and gene expression profiles were determined by DNA microarray analyses. Adipose-derived stromal cells (ASCs) from both sites were isolated and analyzed for their capacity to proliferate, form clones, and differentiate. Chin and knee fat depots expressed a differentHOXcode and could have different embryonic origins. ASCs displayed a different phenotype, with chin-ASCs having the potential to differentiate into brown-like adipocytes, whereas knee-ASCs differentiated into white adipocytes. These results highlighted different features for these two fat sites and indicated that donor site selection might be an important factor to be considered when applying adipose tissue in cell-based therapies.

scholarly journals Bioreactor Processed Stromal Cell Seeding and Cultivation on Decellularized Pericardium Patches for Cardiovascular Use

2020 ◽  
Vol 10 (16) ◽  
pp. 5473
Author(s):  
Roman Matějka ◽  
Miroslav Koňařík ◽  
Jana Štěpanovská ◽  
Jan Lipenský ◽  
Jaroslav Chlupáč ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Stromal Cells ◽  
Subcutaneous Fat ◽  
Adipose Derived Stromal Cells ◽  
Pulsatile Pressure ◽  
Dynamic Cultivation ◽  
Decellularized Tissue ◽  
Static Conditions

(1) Background: Decellularized xenogeneic tissues are promising matrices for developing tissue-engineered cardiovascular grafts. In vitro recellularization of these tissues with stromal cells can provide a better in vivo remodelling and a lower thrombogenicity of the graft. The process of recellularization can be accelerated using a cultivation bioreactor simulating physiological conditions and stimuli. (2) Methods: Porcine pericardium was decellularized using a custom-built decellularization system with an optimized protocol. Autologous porcine adipose-derived stromal cells (PrASCs), isolated from the subcutaneous fat tissue, were used for recellularizing the decellularized pericardium. A custom cultivation bioreactor allowing the fixing of the decellularized tissue into a special cultivation chamber was created. The bioreactor maintained micro-perfusion and pulsatile pressure stimulation in order to promote the ingrowth of PrASCs inside the tissue and their differentiation. (3) Results: The dynamic cultivation promoted the ingrowth of cells into the decellularized tissue. Under static conditions, the cells penetrated only to the depth of 50 µm, whereas under dynamic conditions, the tissue was colonized up to 250 µm. The dynamic cultivation also supported the cell differentiation towards smooth muscle cells (SMCs). In order to ensure homogeneous cell colonization of the decellularized matrices, the bioreactor was designed to allow seeding of the cells from both sides of the tissue prior to the stimulation. In this case, the decellularized tissue was recolonized with cells within 5 days of dynamic cultivation. (4) Conclusions: Our newly designed dynamic bioreactor markedly accelerated the colonization of decellularized pericardium with ASCs and cell differentiation towards the SMC phenotype.

Long-Term Production System of Red Blood Cells Using Human Cord Blood and Stromal Cells

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3211-3211
Author(s):  
Masayoshi Kobune ◽  
Shohei Kikuchi ◽  
Kazuyuki Murase ◽  
Satoshi Iyama ◽  
Tsutomu Sato ◽  
...  
Keyword(s):  
Cord Blood ◽  
Progenitor Cells ◽  
Stromal Cells ◽  
Production System ◽  
Ex Vivo ◽  
Erythroid Progenitor ◽  
Differentiation Potential ◽  
Hematopoietic Stem ◽  
Human Stromal Cells

Abstract Abstract 3211 We have previously shown that primary human stromal cells and hTERT-transduced human stromal cells (hTERT-stromal cells) support cord blood (CB) hematopoietic stem/progenitor cells. However, it is unclear whether human stromal cells maintain the expansion of erythroid progenitor cells without losing erythroid differentiation potential for a long-term ex vivo culture. In an attempt to evaluate the efficacy of human stromal cells, erythroid induction was conducted by SCF, EPO and IGF-1, 2-week after expansion of CB CD34+ cells with or without human stromal cells. The maturation of erythroid cells were evaluated by morphological findings, transferrin receptor (TfR)/glycophorin A (GPA) expression and hemoglobin (Hb) synthesis (MCH, pg/cells). The number of BFU-E upon 2-week coculture with the hTERT-stromal cells was significantly higher than those without hTERT-stromal cells (BFU-E, 639±102 vs. 4078±1935, the initial cell number of BFU-E was 513±10). Hb concentration of erythroblasts that had been derived from coculture with stromal cells, was significantly higher than that derived from stroma-free condition 14 days after erythroid induction (MCH, 0.78±0.11 vs. 2.62±0.12; p<0.05). Moreover, cobblestone area (CA)-forming cells existed beneath stromal layer weekly produced the large number of BFU-E from 4th week to at least 8th week (the total number of BFU-E, 57246±1288)(Figure A). Notably, these BFU-Es derived from CA could simultaneously differentiate into orthophilic erythroblasts with nearly normal Hb synthesis (MHC, 24.5±6.4 pg/cell)(Figure B) and GPA expression. Furthermore, most of these erythroblasts derived from CA underwent enucleation spontaneously after further 7 days culture. Thus, using hTERT-stromal cells, the long-term ex vivo erythroid production could be attained from CB cells. These findings contribute to constructing long-term of ex vivo erythroid production system using human stromal cells. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Comparative Analysis of Mesenchymal Stromal Cells Biological Properties

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Angela De Luca ◽  
Rosanna Verardi ◽  
Arabella Neva ◽  
Patrizia Benzoni ◽  
Elisabetta Crescini ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Adipose Tissue ◽  
Cell Therapy ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Subcutaneous Fat ◽  
Biological Properties ◽  
Human Mscs ◽  
Differentiation Potential ◽  
Tissue Samples

The stromal progenitors of mesodermal cells, mesenchymal stromal cells (MSCs), are a heterogeneous population of plastic adherent fibroblast-like cells with extensive proliferative capacity and differentiation potential. Human MSCs have now been isolated from various tissues including bone marrow, muscle, skin, and adipose tissue, the latter being one of the most suitable cell sources for cell therapy, because of its easy accessibility, minimal morbidity, and abundance of cells. Bone marrow and subcutaneous or visceral adipose tissue samples were collected, digested with collagenase if needed, and seeded in Iscove's medium containing 5% human platelet lysate. Nonadherent cells were removed after 2-3 days and the medium was replaced twice a week. Confluent adherent cells were detached, expanded, and analyzed for several biological properties such as morphology, immunophenotype, growth rate, senescence, clonogenicity, differentiation capacity, immunosuppression, and secretion of angiogenic factors. The results show significant differences between lines derived from subcutaneous fat compared to those derived from visceral fat, such as the higher proliferation rate of the first and the strong induction of angiogenesis of the latter. We are convinced that the identification of the peculiarities of MSCs isolated from different tissues will lead to their more accurate use in cell therapy.

scholarly journals Senescence-associated metabolomic phenotype in primary and iPSC-derived mesenchymal stromal cells

2019 ◽  
Author(s):  
Eduardo Fernandez-Rebollo ◽  
Julia Franzen ◽  
Jonathan Hollmann ◽  
Alina Ostrowska ◽  
Matteo Oliverio ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Replicative Senescence ◽  
Cell Types ◽  
Cellular Aging ◽  
Metabolic Switch ◽  
Differentiation Potential ◽  
Long Term Culture ◽  
Functional Changes

Long-term culture of primary cells is reflected by functional and secretory changes, which ultimately result in replicative senescence. In contrast, induced pluripotent stem cells (iPSCs) do not reveal any signs of cellular aging while in the pluripotency state, whereas little is known how they senesce upon differentiation. Furthermore, it is largely unclear how the metabolome of cells changes during replicative senescence and if such changes are consistent across different cell types. In this study, we have directly compared culture expansion of primary mesenchymal stromal cells (MSCs) and iPSC-derived MSCs (iMSCs) until they reached growth arrest after a mean of 21 and 17 cumulative population doublings, respectively. Both cell types acquired similar changes in morphology, in vitro differentiation potential, up-regulation of senescence-associated beta-galactosidase, and senescence-associated DNA methylation changes. Furthermore, MSCs and iMSCs revealed overlapping gene expression changes during culture expansion, particularly in functional categories related to metabolic processes. We subsequently compared the metabolome of MSCs and iMSCs at early and senescent passages and observed various significant and overlapping senescence-associated changes in both cell types, including down-regulation of nicotinamide ribonucleotide and up-regulation of orotic acid. Replicative senescence of both cell types was consistently reflected by the metabolic switch from oxidative to glycolytic pathways. Taken together, long-term culture of iPSC-derived MSCs evokes very similar molecular and functional changes as observed in primary MSCs. Replicative senescence is associated with a highly reproducible senescence-associated metabolomics phenotype, which may be used to monitor the state of cellular aging.

Transdifferentiation properties of adipocytes in the adipose organ

2009 ◽  
Vol 297 (5) ◽  
pp. E977-E986 ◽  
Author(s):  
Saverio Cinti
Keyword(s):  
Insulin Resistance ◽  
Visceral Fat ◽  
Metabolic Disorders ◽  
Subcutaneous Fat ◽  
Causative Factor ◽  
Brown Adipocytes ◽  
Anatomy And Physiology ◽  
White Adipocytes ◽  
Adipose Organ

Mammals have two types of adipocytes, white and brown, but their anatomy and physiology is different. White adipocytes store lipids, and brown adipocytes burn them to produce heat. Previous descriptions implied their localization in distinct sites, but we demonstrated that they are mixed in many depots, raising the concept of adipose organ. We explain the reason for their cohabitation with the hypothesis of reversible physiological transdifferentiation; they are able to convert one into each other. If needed, the brown component of the organ could increase at the expense of the white component and vice versa. This plasticity is important because the brown phenotype of the organ associates with resistance to obesity and related disorders. Another example of physiological transdifferetiation of adipocytes is offered by the mammary gland; the pregnancy hormonal stimuli seems to trigger a reversible transdifferentiation of adipocytes into milk-secreting epithelial glands. The obese adipose organ is infiltrated by macrophages inducing chronic inflamation that is widely considered as a causative factor for insulin resistance. We showed that the vast majority of macrophages infiltrating the obese organ are arranged around dead adipocytes, forming characteristic crown-like structures. We recently found that visceral fat is more infiltrated than the subcutaneous fat despite a smaller size of visceral adipocytes. This suggests a different susceptibility of visceral and subcutaneous adipocytes to death, raising the concept of smaller critical death size that could be important to explain the key role of visceral fat for the metabolic disorders associated with obesity.

scholarly journals Adipose-Derived Stromal Cells Attenuate Adipose Inflammation in Obesity through Adipocyte Browning and Polarization of M2 Macrophages

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Wen-Chao Zhang ◽  
Feng Qin ◽  
Xiao-Jun Wang ◽  
Zhi-Fei Liu ◽  
Lin Zhu ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Animal Experiments ◽  
Brown Adipocyte ◽  
Metabolic Dysfunction ◽  
M2 Macrophages ◽  
Obese Mice ◽  
Brown Adipocytes ◽  
Adipose Derived Stromal Cells ◽  
Proinflammatory Responses ◽  
Adipose Inflammation

Obesity is a metabolic condition associated with multiple health problems such as endocrine and metabolic dysfunction and chronic inflammation in adipose tissues. In this study, the ADSCs could be stimulated to differentiate into brown adipocyte with rosiglitazone treatment based on the Oil-Red-O staining trial. Furthermore, the multilocular lipid droplets located in the center was increased in differentiated brown adipocytes, and brown fat-associated proteins, UCP1, PPAR-γ, and LPL were highly expressed in brown adipocytes differentiated from ADSCs. Additionally, the results of animal experiments showed that both weight and amount of VLDL and LDL were decreased in the serum of obese mice after transplantation of rosiglitazone-induced brown adipocytes, while the level of HDL increased. Moreover, the proteins associated with lipid metabolism, LPA and UCP1, were downregulated, and the inflammatory response was suppressed through inhibition of the ITGAM/NF-κB-mediated proinflammatory responses and polarization of M2 macrophages. Similarly, the amounts of proinflammatory cytokines, TNF-α, IL-6, and IL-1β were decreased after rosiglitazone-induced brown adipocyte transplantation. On the contrary, anti-inflammatory cytokine IL-10 was significantly increased in both groups of obese mice, with or without brown adipocyte transplantation. Therefore, the adipose-derived stromal cells with induced browning could promote lipid consumption and alternative polarization of M2 macrophages to attenuate adipose inflammation in obesity mouse models, which thus provides a potential therapy for obesity.

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