Characterization and Beige Adipogenic Potential of Human Embryo White Adipose Tissue-Derived Stem Cells

Background/Aims: Brown and beige adipocytes are widely recognized as potential therapeutic targets to treat obesity and related metabolic disorders, and the recruitment of brown and beige adipocytes is an essential aspect that requires attention. Although many methods of activating brown adipocytes or generating beige adipocytes have been reported, the limited number and sources are the biggest challenges. The number of white adipocytes is much greater than the number of brown adipocytes, both in human adults and fetuses. Unfortunately, human adult white adipose tissue-derived stem cell (aWAsc) has little beige adipogenic potential. However, the characteristics and beige adipogenic potential of human embryo-derived white adipose stem cells (eWAsc) still need to be investigated. Methods: To analyze the characteristics and functionality of eWAsc, we analyzed the markers of adipose precursor cells by flow cytometry. Then, differentiation and browning/beiging were induced, and the identifying markers were analyzed by real-time PCR and immunoblot. In addition, more in-depth exploration was performed using RNA-SEQ on eWAsc and aWAsc. Results: eWAsc was isolated from human embryonic white adipose tissue, and aWAsc was isolated from adult white adipose tissue by collagenase treatment. eWAsc has extreme advantages in adipogenesis capacity and browning/beiging ability in comparison to aWAsc, indicating that eWAsc may possess some special regulatory factors to promote the generation of functional brown/beige adipocytes. Greater exploration was enabled by RNA-SEQ, revealing a large number of differences at the transcriptional levels, including 1263 differentially expressed genes, 657 down- and 605 upregulated, in eWAsc compared to aWAsc. Pathway analysis revealed enrichment in cell cycle, TGF-β signaling pathway, DNA replication, and Hippo signaling pathways. Interestingly, the expression levels of C/EBPα, FGF1 and FST gene, which are related to the maturation of adipocytes, Hippo signaling pathway and TGF-β signaling pathway, were significantly higher in eWAsc than in aWAsc. These may be potential candidates and possible regulatory targets for recruiting beige adipocytes in human adipose tissue. Conclusion: Overall, we have demonstrated the molecular characteristics and excellent beige adipogenic potential of eWAsc, providing a new reference for studying human adipocytes.

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Pycnogenol® Induces Browning of White Adipose Tissue through the PKA Signaling Pathway in Apolipoprotein E-Deficient Mice

Journal of Diabetes Research ◽

10.1155/2018/9713259 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11 ◽

Cited By ~ 4

Author(s):

Huiying Cong ◽

Wenxia Zhong ◽

Yiying Wang ◽

Shoichiro Ikuyama ◽

Bin Fan ◽

...

Keyword(s):

Adipose Tissue ◽

Apolipoprotein E ◽

Signaling Pathway ◽

White Adipose Tissue ◽

High Fat Diet ◽

Mrna Level ◽

Antioxidant Properties ◽

Expression Of Genes ◽

Beige Adipocytes ◽

Deficient Mice

Beige adipocytes in white adipose tissue (WAT) have received considerable recognition because of their potential protective effect against obesity. Pycnogenol (PYC), extracted from French maritime pine bark, has anti-inflammatory and antioxidant properties and can improve lipid profiles. However, the effect of PYC on obesity has never been explored. In this study, we investigated the effects of PYC on obesity and WAT browning in apolipoprotein E- (ApoE-) deficient mice. The results showed that PYC treatment clearly reversed body weight and the mass of eWAT gain resulting from a high-cholesterol and high-fat diet (HCD), but no difference in food intake. The morphology results showed that the size of the adipocytes in the PYC-treated mice was obviously smaller than that in the HCD-fed mice. Next, we found that PYC upregulated the expression of genes related to lipolysis (ATGL and HSL), while it decreased the mRNA level of PLIN1. PYC significantly increased the expression of UCP1 and other genes related to beige adipogenesis. Additionally, PYC increased the expression of proteins related to the protein kinase A (PKA) signaling pathway. The findings suggested that PYC decreased obesity by promoting lipolysis and WAT browning. Thus, PYC may be a novel therapeutic target for obesity.

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Hippo-YAP signaling controls lineage differentiation of mouse embryonic stem cells through modulating the formation of super-enhancers

Nucleic Acids Research ◽

10.1093/nar/gkaa482 ◽

2020 ◽

Cited By ~ 1

Author(s):

Xiang Sun ◽

Zhijun Ren ◽

Yixian Cun ◽

Cai Zhao ◽

Xianglin Huang ◽

...

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Signaling Pathway ◽

Embryoid Body ◽

Embryonic Stem ◽

Mouse Embryonic Stem Cells ◽

Hippo Signaling ◽

Rna Seq ◽

Lineage Differentiation ◽

Super Enhancer

Abstract Hippo-YAP signaling pathway functions in early lineage differentiation of pluripotent stem cells, but the detailed mechanisms remain elusive. We found that knockout (KO) of Mst1 and Mst2, two key components of the Hippo signaling in mouse embryonic stem cells (ESCs), resulted in a disruption of differentiation into mesendoderm lineage. To further uncover the underlying regulatory mechanisms, we performed a series of ChIP-seq experiments with antibodies against YAP, ESC master transcription factors and some characterized histone modification markers as well as RNA-seq assays using wild type and Mst KO samples at ES and day 4 embryoid body stage respectively. We demonstrate that YAP is preferentially co-localized with super-enhancer (SE) markers such as Nanog, Sox2, Oct4 and H3K27ac in ESCs. The hyper-activation of nuclear YAP in Mst KO ESCs facilitates the binding of Nanog, Sox2 and Oct4 as well as H3K27ac modification at the loci where YAP binds. Moreover, Mst depletion results in novel SE formation and enhanced liquid-liquid phase-separated Med1 condensates on lineage associated genes, leading to the upregulation of these genes and the distortion of ESC differentiation. Our study reveals a novel mechanism on how Hippo-YAP signaling pathway dictates ESC lineage differentiation.

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Neuronal Modulation of Brown Adipose Activity Through Perturbation of White Adipocyte Lipogenesis

10.1101/324160 ◽

2018 ◽

Author(s):

Adilson Guilherme ◽

David J Pedersen ◽

Felipe Henriques ◽

Alexander H. Bedard ◽

Elizabeth Henchey ◽

...

Keyword(s):

Adipose Tissue ◽

White Adipose Tissue ◽

Fatty Acid Synthase ◽

Sympathetic Neurons ◽

Sympathetic Innervation ◽

Long Distance ◽

Brown Adipocytes ◽

White Adipocyte ◽

Brown Adipose ◽

Beige Adipocytes

ABSTRACTWhite adipose tissue (WAT) secretes factors to communicate with other metabolic organs to maintain energy homeostasis. We previously reported that perturbation of adipocyte de novo lipogenesis (DNL) by deletion of fatty acid synthase (FASN) causes expansion of sympathetic neurons within white adipose tissue (WAT) and the appearance of “beige” adipocytes. Here we report evidence that white adipocyte DNL activity is also coupled to neuronal regulation and thermogenesis in brown adipose tissue (BAT). Induced deletion of FASN in all adipocytes in mature mice (iAdFASNKO) enhanced sympathetic innervation and neuronal activity as well as UCP1 expression in both WAT and BAT. In contrast, selective ablation of FASN in brown adipocytes of mice (iUCP1FASNKO) failed to modulate sympathetic innervation and the thermogenic program in BAT. Surprisingly, DNL in brown adipocytes was also dispensable in maintaining euthermia when UCP1FASNKO mice were cold-exposed. These results indicate that DNL in white adipocytes influences long distance signaling to BAT, which can modify BAT sympathetic innervation and expression of genes involved in thermogenesis.

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Derivation, characterization, and in vitro cell regeneration of canine white adipose tissue-derived mesenchymal stem cells obtained from a mesenteric region

The Journal of Basic and Applied Zoology ◽

10.1186/s41936-021-00222-1 ◽

2021 ◽

Vol 82 (1) ◽

Author(s):

Anirban Mandal ◽

Ajeet Kumar Jha ◽

Dew Biswas ◽

Shyamal Kanti Guha

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

White Adipose Tissue ◽

Stromal Vascular Fraction ◽

Cell Regeneration ◽

Wound Healing Assay ◽

Chain Reaction ◽

Polymerase Chain

Abstract Background The study was conducted to assess the characterization, differentiation, and in vitro cell regeneration potential of canine mesenteric white adipose tissue-derived mesenchymal stem cells (AD-MSCs). The tissue was harvested through surgical incision and digested with collagenase to obtain a stromal vascular fraction. Mesenchymal stem cells isolated from the stromal vascular fraction were characterized through flow cytometry and reverse transcription-polymerase chain reaction. Assessment of cell viability, in vitro cell regeneration, and cell senescence were carried out through MTT assay, wound healing assay, and β-galactosidase assay, respectively. To ascertain the trilineage differentiation potential, MSCs were stained with alizarin red for osteocytes, alcian blue for chondrocytes, and oil o red for adipocytes. In addition, differentiated cells were characterized through a reverse transcription-polymerase chain reaction. Results We observed the elongated, spindle-shaped, and fibroblast-like appearance of cells after 72 h of initial culture. Flow cytometry results showed positive expression for CD44, CD90, and negative expression for CD45 surface markers. Population doubling time was found 18–24 h for up to the fourth passage and 30±0.5 h for the fifth passage. A wound-healing assay was used to determine cell migration rate which was found 136.9 ± 4.7 μm/h. We observed long-term in vitro cell proliferation resulted in MSC senescence. Furthermore, we also found that the isolated cells were capable of differentiating into osteogenic, chondrogenic, and adipogenic lineages. Conclusions Mesenteric white adipose tissue was found to be a potential source for isolation, characterization, and differentiation of MSCs. This study might be helpful for resolving the problems regarding the paucity of information concerning the basic biology of stem cells. The large-scale use of AD-MSCs might be a remedial measure in regenerative medicine.

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Sympathetic Innervation of White Adipose Tissue: to Beige or Not to Beige?

Physiology ◽

10.1152/physiol.00038.2020 ◽

2021 ◽

Vol 36 (4) ◽

pp. 246-255

Author(s):

Heike Münzberg ◽

Elizabeth Floyd ◽

Ji Suk Chang

Keyword(s):

Adipose Tissue ◽

White Adipose Tissue ◽

Metabolic Regulation ◽

Current Knowledge ◽

Sympathetic Innervation ◽

Neuronal Circuits ◽

Brown Adipocytes ◽

White Adipocyte ◽

Obesity Research ◽

Neuronal Regulation

Obesity research progresses in understanding neuronal circuits and adipocyte biology to regulate metabolism. However, the interface of neuro-adipocyte interaction is less studied. We summarize the current knowledge of adipose tissue innervation and interaction with adipocytes and emphasize adipocyte transitions from white to brown adipocytes and vice versa. We further highlight emerging concepts for the differential neuronal regulation of brown/beige versus white adipocyte and the interdependence of both for metabolic regulation.

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CXCL13 inhibits microRNA-23a through PI3K/AKT signaling pathway in adipose tissue derived-mesenchymal stem cells

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2016.07.059 ◽

2016 ◽

Vol 83 ◽

pp. 876-880 ◽

Cited By ~ 6

Author(s):

Zhen-Wei Li ◽

Liang Zhao ◽

Qi-Cai Han ◽

Xu Zhu

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

Signaling Pathway ◽

Akt Signaling ◽

Akt Signaling Pathway

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AT1 receptor antagonist induces thermogenic beige adipocytes in the inguinal white adipose tissue of obese mice

Endocrine ◽

10.1007/s12020-016-1213-1 ◽

2016 ◽

Vol 55 (3) ◽

pp. 786-798 ◽

Cited By ~ 6

Author(s):

Francielle Graus-Nunes ◽

Tamiris Lima Rachid ◽

Felipe de Oliveira Santos ◽

Sandra Barbosa-da-Silva ◽

Vanessa Souza-Mello

Keyword(s):

Adipose Tissue ◽

Receptor Antagonist ◽

White Adipose Tissue ◽

At1 Receptor ◽

Obese Mice ◽

Beige Adipocytes

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Study on the role of JAK/STAT signaling pathway during chicken spermatogonial stem cells generation based on RNA-Seq

Journal of Integrative Agriculture ◽

10.1016/s2095-3119(14)60938-2 ◽

2015 ◽

Vol 14 (5) ◽

pp. 939-948 ◽

Cited By ~ 5

Author(s):

Lei ZHANG ◽

Qi-sheng ZUO ◽

Dong LI ◽

Chao LIAN ◽

Kamel E Ahmed ◽

...

Keyword(s):

Stem Cells ◽

Signaling Pathway ◽

Spermatogonial Stem Cells ◽

Rna Seq ◽

Stat Signaling

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Lats1/2-Mediated Alteration of Hippo Signaling Pathway Regulates the Fate of Bone Marrow-Derived Mesenchymal Stem Cells

BioMed Research International ◽

10.1155/2018/4387932 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11 ◽

Cited By ~ 4

Author(s):

Lang Li ◽

Liang Dong ◽

Yifeng Wang ◽

Xiuhong Zhang ◽

Jie Yan

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Signaling Pathway ◽

Vertical Migration ◽

Transduction Efficiency ◽

Hippo Signaling ◽

Migration Assay ◽

Hippo Signaling Pathway ◽

Low Expression

Bone marrow-derived mesenchymal stem cells (BMSCs) can be used to enhance lung repair in acute respiratory distress syndrome (ARDS); however, the repairing effect is limited by poor homing and retention of BMSCs. The purpose of this study was to investigate whether Lats1 and Lats2-mediated alteration of Hippo signaling pathway could promote the differentiation, proliferation, and migration of BMSCs. BMSCs were transduced by lentiviral vectors for high and low expression of Lats1 and Lats2. The expression levels of Lats1, Lats2, YAP, and 14-3-3, respectively, were assessed to clarify the regulatory effects of Lats1 and Lats2 on Hippo signaling. Osteogenic (Runx2 and OSX) and adipogenic (C/EBPα and PPAR-γ) transcription factors were determined to clarify the effects of Hippo signaling on BMSCs differentiation. The effects of Hippo signaling on BMSCs proliferation and horizontal and vertical migration were also measured by CCK-8, scratch assay, and Transwell migration assay, respectively. Lentiviral transduction efficiency could reach 93.11%–97.14%. High and low expression of Lats1 and Lats2 could activate and inhibit the Hippo signaling pathway, respectively. High and low expression of Lats1 and Lats2 could inhibit and promote BMSCs differentiation into osteoblasts and adipocytes. High and low expression of Lats1 and Lats2 could inhibit and promote BMSCs proliferation and horizontal and vertical migration, respectively. Our studies suggest that Lats1/2-meidiated inhibition of Hippo signaling in BMSCs may optimize their effects of tissue repair in ARDS, suggesting a novel strategy for enhancing disease therapeutics.

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