scholarly journals Chibby Promotes Adipocyte Differentiation through Inhibition of β-Catenin Signaling

2007 ◽  
Vol 27 (12) ◽  
pp. 4347-4354 ◽  
Author(s):  
Feng-Qian Li ◽  
Amar M. Singh ◽  
Adaobi Mofunanya ◽  
Damon Love ◽  
Naohiro Terada ◽  
...  
Keyword(s):  
Stem Cells ◽  
Adipocyte Differentiation ◽  
Adipogenic Differentiation ◽  
Ectopic Expression ◽  
Embryonic Stem ◽  
Dominant Negative ◽  
Loss Of Function ◽  
Embryonic Fibroblasts ◽  
Protein Levels ◽  
Canonical Wnt

ABSTRACT The canonical Wnt/β-catenin signaling pathway plays diverse roles in embryonic development and disease. Activation of this pathway, likely by Wnt-10b, has been shown to inhibit adipogenesis in cultured 3T3-L1 preadipocytes and in mice. Here, we report that the β-catenin antagonist Chibby (Cby) is required for adipocyte differentiation. Cby is expressed in adipose tissue in mice, and Cby protein levels increase during adipogenic differentiation of 3T3-L1 cells. Ectopic expression of Cby induces spontaneous differentiation of these cells into mature adipocytes to an extent similar to that of dominant-negative Tcf-4. In contrast, depletion of Cby by RNA interference potently blocks adipogenesis of 3T3-L1 and mouse embryonic stem cells. In support of this, embryonic fibroblasts obtained from Cby-deficient embryos display attenuated differentiation to the adipogenic lineage. Mechanistically, Cby promotes adipocyte differentiation, in part by inhibiting β-catenin, since gain or loss of function of Cby influences β-catenin signaling in 3T3-L1 cells. Our results therefore establish Cby as a novel proadipogenic factor required for adipocyte differentiation.

Regulation of adipocyte differentiation of 3T3-L1 cells by PDZRN3

2013 ◽  
Vol 304 (11) ◽  
pp. C1091-C1097 ◽  
Author(s):  
Takeshi Honda ◽  
Aiko Ishii ◽  
Makoto Inui
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipocyte Differentiation ◽  
Early Stage ◽  
Adipogenic Differentiation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels ◽  
Upstream Regulator ◽  
Pparγ Expression

PDZRN3, a member of the PDZRN (or LNX) family of proteins, is essential for the differentiation of mesenchymal stem cells into myotubes, but it plays an inhibitory role in the differentiation of these cells into osteoblasts. Given that mesenchymal stem cells also differentiate into adipocytes, we examined the possible role of PDZRN3 in adipogenesis in mouse 3T3-L1 preadipocytes. The expression of PDZRN3 decreased at both the mRNA and protein levels during adipogenic differentiation. RNAi-mediated depletion of PDZRN3 enhanced the differentiation of 3T3-L1 cells into adipocytes as assessed on the basis of lipid accumulation. The upregulation of aP2 and CCAAT/enhancer-binding protein (C/EBP)-β during adipocyte differentiation was also enhanced in the PDZRN3-depleted cells, as was the induction of peroxisome proliferator-activated receptor-γ (PPARγ), an upstream regulator of aP2 and C/EBPα, at both the mRNA and protein levels. Among transcription factors that control the expression of PPARγ, we found that STAT5b, but not STAT5a, was upregulated in PDZRN3-depleted cells at both mRNA and protein levels. Tyrosine phosphorylation of STAT5b, but not that of STAT5a, was also enhanced at an early stage of differentiation by PDZRN3 depletion. In addition, the expression of C/EBPβ during the induction of differentiation was enhanced at the mRNA and protein levels in PDZRN3-depleted cells. Our results thus suggest that PDZRN3 negatively regulates adipogenesis in 3T3-L1 cells through downregulation of STAT5b and C/EBPβ and consequent suppression of PPARγ expression.

Involvement of PP2A methylation in the adipogenic differentiation of bone marrow-derived mesenchymal stem cell

2020 ◽  
Vol 168 (6) ◽  
pp. 643-650
Author(s):  
Shunta Ikeda ◽  
Shunya Tsuji ◽  
Takashi Ohama ◽  
Koichi Sato
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Protein Phosphatase ◽  
Adipocyte Differentiation ◽  
Tumour Progression ◽  
Adipogenic Differentiation ◽  
Tumour Microenvironment ◽  
Multipotent Stem Cells ◽  
Protein Levels ◽  
Phosphatase 2A

Abstract Bone marrow-derived mesenchymal stem cells (BM-MSCs) are multipotent stem cells with ability to self-replicate and differentiate into mesodermal derivatives, such as adipocytes and osteoblasts. BM-MSCs are a critical component of the tumour microenvironment. They support tumour progression by recruiting additional BM-MSCs and by differentiating into myofibroblasts (also called cancer-associated fibroblasts). Protein phosphatase 2A (PP2A) is an essential serine/threonine protein phosphatase that regulates a broad range of cellular signalling. PP2A forms a heterotrimer to dephosphorylate specific substrates. The reversible methylesterification (methylation) of Leu309 in the catalytic subunit of PP2A (PP2Ac) regulates biogenesis of the PP2A holoenzyme. It is unknown whether the methylation of PP2Ac plays a role in BM-MSC differentiation. Our experiments determined that protein levels of PP2A subunits and PP2A methyltransferase (LCMT-1) are significantly altered during differentiation. PP2Ac methylation levels in BM-MSCs decrease over time in response to an adipogenic differentiation stimulus. However, blockage of PP2A demethylation using the PP2A dimethyl-esterase inhibitors enhanced adipocyte differentiation. This suggests that PP2Ac demethylation is involved in adipocyte differentiation resistance. The results of our study provide a greater understanding of the regulation of BM-MSCs differentiation by PP2A holoenzyme.

scholarly journals Epigenetic Regulation of Mesenchymal Stem Cells: A Focus on Osteogenic and Adipogenic Differentiation

2011 ◽  
Vol 2011 ◽  
pp. 1-18 ◽  
Author(s):  
Chad M. Teven ◽  
Xing Liu ◽  
Ning Hu ◽  
Ni Tang ◽  
Stephanie H. Kim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Epigenetic Regulation ◽  
Adult Stem Cells ◽  
Es Cells ◽  
Adipogenic Differentiation ◽  
Embryonic Stem ◽  
Cell Types ◽  
Differentiation Potential ◽  
Msc Differentiation

Stem cells are characterized by their capability to self-renew and terminally differentiate into multiple cell types. Somatic or adult stem cells have a finite self-renewal capacity and are lineage-restricted. The use of adult stem cells for therapeutic purposes has been a topic of recent interest given the ethical considerations associated with embryonic stem (ES) cells. Mesenchymal stem cells (MSCs) are adult stem cells that can differentiate into osteogenic, adipogenic, chondrogenic, or myogenic lineages. Owing to their ease of isolation and unique characteristics, MSCs have been widely regarded as potential candidates for tissue engineering and repair. While various signaling molecules important to MSC differentiation have been identified, our complete understanding of this process is lacking. Recent investigations focused on the role of epigenetic regulation in lineage-specific differentiation of MSCs have shown that unique patterns of DNA methylation and histone modifications play an important role in the induction of MSC differentiation toward specific lineages. Nevertheless, MSC epigenetic profiles reflect a more restricted differentiation potential as compared to ES cells. Here we review the effect of epigenetic modifications on MSC multipotency and differentiation, with a focus on osteogenic and adipogenic differentiation. We also highlight clinical applications of MSC epigenetics and nuclear reprogramming.

scholarly journals Ethanol Inactivated Mouse Embryonic Fibroblasts Maintain the Self-Renew and Proliferation of Human Embryonic Stem Cells

PLoS ONE ◽  
2015 ◽  
Vol 10 (6) ◽  
pp. e0130332 ◽  
Author(s):  
Boxian Huang ◽  
Song Ning ◽  
Lili Zhuang ◽  
Chunyan Jiang ◽  
Yugui Cui ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
The Self ◽  
Mouse Embryonic Fibroblasts ◽  
Embryonic Fibroblasts

scholarly journals Establishment and Identification of a CiPSC Lineage Reprogrammed from FSP-tdTomato Mouse Embryonic Fibroblasts (MEFs)

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Ruiping Chen ◽  
Wenxiu Xie ◽  
Baomei Cai ◽  
Yue Qin ◽  
Chuman Wu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Small Molecule ◽  
Fluorescent Protein ◽  
Day Treatment ◽  
Tracking System ◽  
Embryonic Stem ◽  
Mouse Embryonic Fibroblasts ◽  
Embryonic Fibroblasts ◽  
Underlying Mechanisms

Safety issues associated with transcription factors or viruses may be avoided with the use of chemically induced pluripotent stem cells (CiPSCs), thus promoting their clinical application. Previously, we had successfully developed and standardized an induction method using small-molecule compound, with simple operation, uniform induction conditions, and clear constituents. In order to verify that the CiPSCs were indeed reprogrammed from mouse embryonic fibroblasts (MEFs), and further explore the underlying mechanisms, FSP-tdTomato mice were used to construct a fluorescent protein-tracking system of MEFs, for revealing the process of CiPSC reprogramming. CiPSCs were identified by morphological analysis, mRNA, and protein expression of pluripotency genes, as well as teratoma formation experiments. Results showed that after 40-day treatment of tdTomato-MEFs with small-molecule compounds, the cells were presented with prominent nucleoli, high core-to-cytoplasmic ratio, round shape, group and mass arrangement, and high expression of pluripotency gene. These cells could differentiate into three germ layer tissues in vivo. As indicated by the above results, tdTomato-MEFs could be reprogrammed into CiPSCs, a lineage that possesses pluripotency similar to mouse embryonic stem cells (mESCs), with the use of small-molecule compounds. The establishment of CiPSC lineage, tracked by fluorescent protein, would benefit further studies exploring its underlying mechanisms. With continuous expression of fluorescent proteins during cellular differentiation, this cell lineage could be used for tracking CiPSC transplantation and differentiation into functional cells.

scholarly journals A mini review on production of pluripotency factors (Oct4, Sox2, Klf4 and c-Myc) through recombinant protein technology

2020 ◽  
Vol 5 (1) ◽  
pp. 1-4 ◽  
Author(s):  
David Septian Sumanto Marpaung ◽  
Ayu Oshin Yap Sinaga
Keyword(s):  
Stem Cells ◽  
Transcription Factors ◽  
Embryonic Stem Cells ◽  
Pluripotent Stem Cells ◽  
Ectopic Expression ◽  
Embryonic Stem ◽  
Cell Types ◽  
Induced Pluripotency ◽  
Pluripotency Factors ◽  
Induced Pluripotent

The four transcription factors OCT4, SOX2, KLF4 and c-MYC are highly expressed in embryonic stem cells (ESC) and their overexpression can induce pluripotency, the ability to differentiate into all cell types of an organism. The ectopic expression such transcription factors could reprogram somatic stem cells become induced pluripotency stem cells (iPSC), an embryonic stem cells-like. Production of recombinant pluripotency factors gain interests due to high demand from generation of induced pluripotent stem cells in regenerative medical therapy recently. This review will focus on demonstrate the recent advances in recombinant pluripotency factor production using various host.

MicroRNAs: Crucial Players in the Differentiation of Human Pluripotent and Multipotent Stem Cells into Functional Hepatocyte-Like Cells

2021 ◽  
Vol 16 ◽  
Author(s):  
Hao Xu ◽  
Liying Wu ◽  
Guojia Yuan ◽  
Xiaolu Liang ◽  
Xiaoguang Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Liver Disease ◽  
Pluripotent Stem Cells ◽  
Disease Modeling ◽  
Critical Role ◽  
Ectopic Expression ◽  
Embryonic Stem ◽  
The Body

: Hepatic disease negatively impacts liver function and metabolism. Primary human hepatocytes are the gold standard for the prediction and successful treatment of liver disease. However, the sources of hepatocytes for drug toxicity testing and disease modeling are limited. To overcome this issue, pluripotent stem cells (PSCs) have emerged as an alternative strategy for liver disease therapy. Human PSCs, including embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC) can self-renew and give rise to all cells of the body. Human PSCs are attractive cell sources for regenerative medicine, tissue engineering, drug discovery, and developmental studies. Several recent studies have shown that mesenchymal stem cells (MSCs) can also differentiate (or trans-differentiate) into hepatocytes. Differentiation of human PSCs and MSCs into functional hepatocyte-like cells (HLCs) opens new strategies to study genetic diseases, hepatotoxicity, infection of hepatotropic viruses, and analyze hepatic biology. Numerous in vitro and in vivo differentiation protocols have been established to obtain human PSCs/MSCs-derived HLCs and mimic their characteristics. It was recently discovered that microRNAs (miRNAs) play a critical role in controlling the ectopic expression of transcription factors and governing the hepatocyte differentiation of human PSCs and MSCs. In this review, we focused on the role of miRNAs in the differentiation of human PSCs and MSCs into hepatocytes.

scholarly journals RPTPμ tyrosine phosphatase promotes adipogenic differentiation via modulation of p120 catenin phosphorylation

2011 ◽  
Vol 22 (24) ◽  
pp. 4883-4891 ◽  
Author(s):  
Won Kon Kim ◽  
Hyeyun Jung ◽  
Eun Young Kim ◽  
Do Hyung Kim ◽  
Yee Sook Cho ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Adipocyte Differentiation ◽  
Adipogenic Differentiation ◽  
Tyrosine Phosphatase ◽  
Ectopic Expression ◽  
Protein Tyrosine Phosphatases ◽  
P120 Catenin ◽  
Protein Tyrosine ◽  
Functional Roles ◽  
Novel Target

Adipocyte differentiation can be regulated by the combined activity of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). In particular, PTPs act as key regulators in differentiation-associated signaling pathways. We recently found that receptor-type PTPμ (RPTPμ) expression is markedly increased during the adipogenic differentiation of 3T3-L1 preadipocytes and mesenchymal stem cells. Here, we investigate the functional roles of RPTPμ and the mechanism of its involvement in the regulation of signal transduction during adipogenesis of 3T3-L1 cells. Depletion of endogenous RPTPμ by RNA interference significantly inhibited adipogenic differentiation, whereas RPTPμ overexpression led to an increase in adipogenic differentiation. Ectopic expression of p120 catenin suppressed adipocyte differentiation, and the decrease in adipogenesis by p120 catenin was recovered by introducing RPTPμ. Moreover, RPTPμ induced a decrease in the cytoplasmic p120 catenin expression by reducing its tyrosine phosphorylation level, consequently leading to enhanced translocation of Glut-4 to the plasma membrane. On the basis of these results, we propose that RPTPμ acts as a positive regulator of adipogenesis by modulating the cytoplasmic p120 catenin level. Our data conclusively demonstrate that differentiation into adipocytes is controlled by RPTPμ, supporting the utility of RPTPμ and p120 catenin as novel target proteins for the treatment of obesity.

431. Importin proteins and their role in maintenance of the stem cell state

2008 ◽  
Vol 20 (9) ◽  
pp. 111
Author(s):  
J. C. Young ◽  
Y. Miyamoto ◽  
A. Major ◽  
V. L. Dias ◽  
D. A. Jans ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Embryonic Stem ◽  
Distribution Patterns ◽  
Embryoid Bodies ◽  
Dominant Negative ◽  
Subcellular Localisation ◽  
Mrna Levels ◽  
Pluripotency Marker

The importin (IMP) family of proteins mediates transport into the nucleus for many proteins larger than 40 kD. Through differential cargo recognition, IMPs regulate cellular events by controlling nuclear access of transcription factors and chromatin remodelling agents. During spermatogenesis, many IMPs change expression and localisation in a manner concordant with specific stages of spermatogenic development. To assess the potential role of IMPs in the transition between the stem cell and subsequent differentiation, we undertook analysis of the expression and subcellular localisation of several key murine IMPs in both pluripotent embryonic stem cells (mESCs) and embryoid bodies (EBs). All of the IMPs analysed (IMPα2, 3, 4, IMPβ1 and IMP5) were detected in undifferentiated mESCs by immunofluorescence, and each exhibited distinctive nucleocytoplasmic distribution patterns. Subcellular localisation of most IMPs altered after 10 days of mESC differentiation as EBs. This was paralleled by changes in the mRNA levels of IMPα1–4, IMPα6, IMPβ1 and IMP5, concomitant with alterations in the expression level of the pluripotency marker, Oct3/4. Reducing IMP-dependent nuclear import through overexpression of specific dominant-negative IMP constructs led to alterations in import or production of Oct3/4 protein, depending on the specific IMP. These findings indicate that IMPs may play very specific but distinct roles in cell fate choice between maintenance of pluri/multipotency and commitment to differentiation in ESCs and potentially in spermatogenesis or other organs that contain stem cells.

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