Comparative gene array analysis of progenitor cells from human paired deep neck and subcutaneous adipose tissue

Tews, Daniel; Schwar, V.; Scheithauer, Marc O.; Weber, Theresia; Fromme, Tobias; Klingenspor, Martin; Barth, Thomas F.E.; Möller, Peter; Holzmann, Karlheinz; Debatin, Klaus‐Michael; Fischer‐Posovszky, Pamela; Wabitsch, Martin

doi:10.1016/j.mce.2014.07.011

Cited by 40 publications

(45 citation statements)

References 39 publications

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“…One of the major sites that contain active BAT in humans is located in the neck, particularly in its deep regions [14,46]. When we compared SC and DN adipocyte progenitors from human neck, the latter had greater browning potential, in accordance with previous findings [18,36,47,48]. On the other hand, SC hASCs were also able to build up a significant thermogenic competency.…”

Section: Discussionsupporting

confidence: 87%

“…We intended to examine global gene expression patterns of hASC-derived white and brown adipocytes and undifferentiated progenitors cultivated from paired DN and SC adipose tissue biopsies. Before doing that, we aimed to validate if adipocytes differentiated for two weeks from the aforementioned hASCs isolated from four individuals have different functional properties as described in previous studies [18,36]. Basal and proton leak mitochondrial respiration of DN adipocytes was significantly elevated as compared to the SC adipocytes regardless of the obtained protocol ( Figure S1A).…”

Section: Dn and Sc Progenitors Have Similar Surface Markers And Adipomentioning

confidence: 78%

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

Tóth

Arianti

Shaw

et al. 2020

Cells

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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.

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Section: Discussionsupporting

confidence: 87%

Section: Dn and Sc Progenitors Have Similar Surface Markers And Adipomentioning

confidence: 78%

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

Tóth

Arianti

Shaw

et al. 2020

Cells

View full text Add to dashboard Cite

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“…2d). Consistent with a recent report 23 , we found that the expression of contactin-associated protein-like 3 ( CNTNAP3 ), leucine-rich repeat-containing 17 ( LRRC17 ), regulator of G-protein signaling 7 binding protein ( RGS7BP ), phosphodiesterase 5A, cGMP-specific ( PDE5A ), and ATP-binding cassette, subfamily A, member 9 ( ABCA9 ) was higher in the clonal brown preadipocyte lines than that in the clonal white preadipocyte lines (Supplementary Table 2). This separation at the gene-expression level was further validated by volcano plot analysis, which showed that the degree of difference in brown and white adipocyte transcriptomes was comparable between undifferentiated and differentiated states (Fig.…”

supporting

confidence: 93%

Genetic and functional characterization of clonally derived adult human brown adipocytes

Shinoda

Luijten

Hasegawa

et al. 2015

Nat Med

364

353

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Brown adipose tissue (BAT) acts in mammals as a natural defense system against hypothermia, and its activation to a state of increased energy expenditure is believed to protect against the development of obesity. Even though the existence of BAT in adult humans has been widely appreciated1–8, its cellular origin and molecular identity remain elusive largely because of high cellular heterogeneity within various adipose tissue depots. To understand the nature of adult human brown adipocytes at single cell resolution, we isolated clonally derived adipocytes from stromal vascular fractions of adult human BAT from two individuals and globally analyzed their molecular signatures. We used RNA sequencing followed by unbiased genome-wide expression analyses and found that a population of uncoupling protein 1 (UCP1)-positive human adipocytes possessed molecular signatures resembling those of a recruitable form of thermogenic adipocytes (that is, beige adipocytes). In addition, we identified molecular markers that were highly enriched in UCP1-positive human adipocytes, a set that included potassium channel K3 (KCNK3) and mitochondrial tumor suppressor 1 (MTUS1). Further, we functionally characterized these two markers using a loss-of-function approach and found that KCNK3 and MTUS1 were required for beige adipocyte differentiation and thermogenic function. The results of this study present new opportunities for human BAT research, such as facilitating cell-based disease modeling and unbiased screens for thermogenic regulators.

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Section: Dn and Sc Progenitors Have Similar Surface Markers And Adipomentioning

confidence: 85%

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

Tóth

Arianti

Shaw

et al. 2020

Preprint

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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.

show abstract

Comparative gene array analysis of progenitor cells from human paired deep neck and subcutaneous adipose tissue

Cited by 40 publications

References 39 publications

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

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

Genetic and functional characterization of clonally derived adult human brown adipocytes

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

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