X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

3T3-L1

RRID:CVCL_0123

Organism

Mus musculus

Comments

Discontinued: ATCC; CCL-92.1. Breed/subspecies: Swiss albino. DT Created: 04-04-12; Last updated: 24-05-19; Version: 21

Proper Citation

ATCC Cat# CCL-92.1, RRID:CVCL_0123

Category

Spontaneously immortalized cell line DT Created: 04-04-12; Last updated: 24-05-19; Version: 21

Sex

DT Created: 04-04-12; Last updated: 24-05-19; Version: 21

Synonyms

3T3 L1, 3T3L1, 3T3-L1 ad, NIH-3T3-L1, NIH3T3-L1 DT Created: 04-04-12, Last updated: 24-05-19, Version: 21

Vendor

ATCC

Cat Num

CCL-92.1

Cross References

BTO; BTO:0000011 CLO; CLO_0001352 EFO; EFO_0001084 EFO; EFO_0001223 MCCL; MCC:0000015 CLDB; cl71 CLDB; cl72 CLDB; cl73 AddexBio; P0011002/407 ATCC; CL-173 ATCC; CCL-92.1 BCRC; 60159 BCRJ; 0019 CCRID; 3111C0001CCC000155 CCRID; 3131C0001000300011 CCRID; 3142C0001000000146 CCRID; 3153C0001000000020 CCTCC; GDC0180 ChEMBL-Cells; CHEMBL3307630 ChEMBL-Targets; CHEMBL614510 CLS; 400103/p821_3T3-Swiss_albino ECACC; 86052701 ENCODE; ENCBS366WMO ENCODE; ENCBS666CGP IBRC; C10152 IZSLER; BS CL 100 JCRB; IFO50416 JCRB; JCRB9014 KCB; KCB 92010YJ KCLB; 10092.1 Lonza; 677 Lonza; 1083 MeSH; D041721 PRIDE; PXD001063 PRIDE; PXD001529 PRIDE; PXD003696 TOKU-E; 331 Wikidata; Q4636414 DT Created: 04-04-12; Last updated: 24-05-19; Version: 21

Hierarchy

DT Created: 04-04-12; Last updated: 24-05-19; Version: 21

Combined Human Genome-wide RNAi and Metabolite Analyses Identify IMPDH as a Host-Directed Target against Chlamydia Infection.

  • Rother M
  • Cell Host Microbe
  • 2018 May 9

Literature context:


Abstract:

Chlamydia trachomatis (Ctr) accounts for >130 million human infections annually. Since chronic Ctr infections are extremely difficult to treat, there is an urgent need for more effective therapeutics. As an obligate intracellular bacterium, Ctr strictly depends on the functional contribution of the host cell. Here, we combined a human genome-wide RNA interference screen with metabolic profiling to obtain detailed understanding of changes in the infected cell and identify druggable pathways essential for Ctr growth. We demonstrate that Ctr shifts the host metabolism toward aerobic glycolysis, consistent with increased biomass requirement. We identify key regulator complexes of glucose and nucleotide metabolism that govern Ctr infection processes. Pharmacological targeting of inosine-5'-monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme in guanine nucleotide biosynthesis, efficiently inhibits Ctr growth both in vitro and in vivo. These results highlight the potency of genome-scale functional screening for the discovery of drug targets against bacterial infections.

Funding information:
  • Wellcome Trust - 094879(United Kingdom)

PCYT1A Regulates Phosphatidylcholine Homeostasis from the Inner Nuclear Membrane in Response to Membrane Stored Curvature Elastic Stress.

  • Haider A
  • Dev. Cell
  • 2018 May 21

Literature context:


Abstract:

Cell and organelle membranes consist of a complex mixture of phospholipids (PLs) that determine their size, shape, and function. Phosphatidylcholine (PC) is the most abundant phospholipid in eukaryotic membranes, yet how cells sense and regulate its levels in vivo remains unclear. Here we show that PCYT1A, the rate-limiting enzyme of PC synthesis, is intranuclear and re-locates to the nuclear membrane in response to the need for membrane PL synthesis in yeast, fly, and mammalian cells. By aligning imaging with lipidomic analysis and data-driven modeling, we demonstrate that yeast PCYT1A membrane association correlates with membrane stored curvature elastic stress estimates. Furthermore, this process occurs inside the nucleus, although nuclear localization signal mutants can compensate for the loss of endogenous PCYT1A in yeast and in fly photoreceptors. These data suggest an ancient mechanism by which nucleoplasmic PCYT1A senses surface PL packing defects on the inner nuclear membrane to control PC homeostasis.

Funding information:
  • Canadian Institutes of Health Research - MOP-312268(Canada)

Elevated (Pro)renin Receptor Expression Contributes to Maintaining Aerobic Metabolism in Growth Hormone Deficiency.

  • Seki Y
  • J Endocr Soc
  • 2018 Mar 1

Literature context:


Abstract:

Context: Growth hormone deficiency (GHD) leads to obesity and may induce tissue hypoxia. As (pro)renin receptor [(P)RR] is reported to contribute to the aerobic metabolism by stabilizing pyruvate dehydrogenase (PDH), it may play a substantial role in GHD. Objective: We aimed to investigate serum soluble (P)RR [s(P)RR] concentration, the origin of s(P)RR, and significance of (P)RR in GHD. Design Setting and Participants: Serum s(P)RR concentration was examined in 72 patients with pituitary diseases, including 32 patients with severe GHD (SGHD) and after GH replacement in 16 SGHD patients. Leptin-deficient ob/ob obese mice were treated with pegvisomant, a GH receptor antagonist, to explore the source of elevated serum s(P)RR in GHD. Adipocytes were cultured with 5% O2 to examine the effects of hypoxia. Results: Serum s(P)RR concentration was higher in patients with SGHD than in those without SGHD. Obesity was the important determinant of s(P)RR concentration. Serum s(P)RR concentration significantly decreased after GH replacement in SGHD patients. (P)RR mRNA expression was increased specifically in the adipose tissue (AT) of pegvisomant-treated obese mice compared with that of control obese mice. Hypoxia in cultured adipocytes increased (P)RR expression without affecting the PDH E1 β subunit (PDHB) expression; however, with (P)RR knockdown by small interfering RNA, hypoxia significantly decreased the expression of PDHB. Conclusion: GHD patients showed increased serum s(P)RR concentration, possibly caused by obesity and hypoxia. (P)RR expression in AT of GHD patients may be elevated to help maintain aerobic metabolism under hypoxia. Thus, the elevated serum s(P)RR level may reflect hypoxia in ATs.

Funding information:
  • NIGMS NIH HHS - R01 GM093000(United States)

Glucocorticoids Suppress the Browning of Adipose Tissue via miR-19b in Male Mice.

  • Lv YF
  • Endocrinology
  • 2018 Jan 1

Literature context:


Abstract:

Physiological levels of glucocorticoids (GCs) are required for proper metabolic control, and excessive GC action has been linked to a variety of pandemic metabolic diseases. MicroRNA (miRNA)-19b plays a critical role in the pathogenesis of GC-induced metabolic diseases. This study explored the potential of miRNA-based therapeutics targeting adipose tissue. Our results showed that overexpressed miR-19b in stromal vascular fraction (SVF) cells derived from subcutaneous adipose tissue had the same effects as dexamethasone (DEX) treatment on the inhibition of adipose browning and oxygen consumption rate. The inhibition of miR-19b blocked DEX-mediated suppression of the expression of browning marker genes as well as the oxygen consumption rate in differentiated SVF cells derived from subcutaneous and brown adipose tissue. Overexpressed miR-19b in SVF cells derived from brown adipose tissue had the same effects as DEX treatment on the inhibition of brown adipose differentiation and energy expenditure. Glucocorticoids transcriptionally regulate the expression of miR-19b via a GC receptor-mediated direct DNA binding mechanism. This study confirmed that miR-19b is an essential target for GC-mediated control of adipose tissue browning. It is hoped that the plasticity of the adipose organ can be exploited in the next generation of therapeutic strategies to combat the increasing incidence of metabolic diseases, including obesity and diabetes.

Ccdc3: A New P63 Target Involved in Regulation Of Liver Lipid Metabolism.

  • Liao W
  • Sci Rep
  • 2017 Aug 21

Literature context:


Abstract:

TAp63, a member of the p53 family, has been shown to regulate energy metabolism. Here, we report coiled coil domain-containing 3 (CCDC3) as a new TAp63 target. TAp63, but not ΔNp63, p53 or p73, upregulates CCDC3 expression by directly binding to its enhancer region. The CCDC3 expression is markedly reduced in TAp63-null mouse embryonic fibroblasts and brown adipose tissues and by tumor necrosis factor alpha that reduces p63 transcriptional activity, but induced by metformin, an anti-diabetic drug that activates p63. Also, the expression of CCDC3 is positively correlated with TAp63 levels, but conversely with ΔNp63 levels, during adipocyte differentiation. Interestingly, CCDC3, as a secreted protein, targets liver cancer cells and increases long chain polyunsaturated fatty acids, but decreases ceramide in the cells. CCDC3 alleviates glucose intolerance, insulin resistance and steatosis formation in transgenic CCDC3 mice on high-fat diet (HFD) by reducing the expression of hepatic PPARγ and its target gene CIDEA as well as other genes involved in de novo lipogenesis. Similar results are reproduced by hepatic expression of ectopic CCDC3 in mice on HFD. Altogether, these results demonstrate that CCDC3 modulates liver lipid metabolism by inhibiting liver de novo lipogenesis as a downstream player of the p63 network.

Ciliary Hedgehog Signaling Restricts Injury-Induced Adipogenesis.

  • Kopinke D
  • Cell
  • 2017 Jul 13

Literature context:


Abstract:

Injured skeletal muscle regenerates, but with age or in muscular dystrophies, muscle is replaced by fat. Upon injury, muscle-resident fibro/adipogenic progenitors (FAPs) proliferated and gave rise to adipocytes. These FAPs dynamically produced primary cilia, structures that transduce intercellular cues such as Hedgehog (Hh) signals. Genetically removing cilia from FAPs inhibited intramuscular adipogenesis, both after injury and in a mouse model of Duchenne muscular dystrophy. Blocking FAP ciliation also enhanced myofiber regeneration after injury and reduced myofiber size decline in the muscular dystrophy model. Hh signaling through FAP cilia regulated the expression of TIMP3, a secreted metalloproteinase inhibitor, that inhibited MMP14 to block adipogenesis. A pharmacological mimetic of TIMP3 blocked the conversion of FAPs into adipocytes, pointing to a strategy to combat fatty degeneration of skeletal muscle. We conclude that ciliary Hh signaling by FAPs orchestrates the regenerative response to skeletal muscle injury.

Funding information:
  • NIAMS NIH HHS - R01 AR054396()
  • NIGMS NIH HHS - R01 GM095941()

Dynamic Rewiring of Promoter-Anchored Chromatin Loops during Adipocyte Differentiation.

  • Siersbæk R
  • Mol. Cell
  • 2017 May 4

Literature context:


Abstract:

Interactions between transcriptional promoters and their distal regulatory elements play an important role in transcriptional regulation; however, the extent to which these interactions are subject to rapid modulations in response to signals is unknown. Here, we use promoter capture Hi-C to demonstrate a rapid reorganization of promoter-anchored chromatin loops within 4 hr after inducing differentiation of 3T3-L1 preadipocytes. The establishment of new promoter-enhancer loops is tightly coupled to activation of poised (histone H3 lysine 4 mono- and dimethylated) enhancers, as evidenced by the acquisition of histone H3 lysine 27 acetylation and the binding of MED1, SMC1, and P300 proteins to these regions, as well as to activation of target genes. Intriguingly, formation of loops connecting activated enhancers and promoters is also associated with extensive recruitment of corepressors such as NCoR and HDACs, indicating that this class of coregulators may play a previously unrecognized role during enhancer activation.

Hypoxia-Inducible Lipid Droplet-Associated Is Not a Direct Physiological Regulator of Lipolysis in Adipose Tissue.

  • Dijk W
  • Endocrinology
  • 2017 May 1

Literature context:


Abstract:

Triglycerides are stored in specialized organelles called lipid droplets. Numerous proteins have been shown to be physically associated with lipid droplets and govern their function. Previously, the protein hypoxia-inducible lipid droplet-associated (HILPDA) was localized to lipid droplets and was suggested to inhibit triglyceride lipolysis in hepatocytes. We confirm the partial localization of HILPDA to lipid droplets and show that HILPDA is highly abundant in adipose tissue, where its expression is controlled by the peroxisome proliferator-activated receptor γ and by β-adrenergic stimulation. Levels of HILPDA markedly increased during 3T3-L1 adipocyte differentiation. Nevertheless, silencing of Hilpda using small interfering RNA or overexpression of Hilpda using adenovirus did not show a clear impact on 3T3-L1 adipogenesis. Following β-adrenergic stimulation, the silencing of Hilpda in adipocytes did not significantly alter the release of nonesterified fatty acids (NEFA) and glycerol. By contrast, adenoviral-mediated overexpression of Hilpda modestly attenuated the release of NEFA from adipocytes following β-adrenergic stimulation. In mice, adipocyte-specific inactivation of Hilpda had no effect on plasma levels of NEFA and glycerol after fasting, cold exposure, or pharmacological β-adrenergic stimulation. In addition, other relevant metabolic parameters were unchanged by adipocyte-specific inactivation of Hilpda. Taken together, we find that HILPDA is highly abundant in adipose tissue, where its levels are induced by peroxisome proliferator-activated receptor γ and β-adrenergic stimulation. In contrast to the reported inhibition of lipolysis by HILPDA in hepatocytes, our data do not support an important direct role of HILPDA in the regulation of lipolysis in adipocytes in vivo and in vitro.

Funding information:
  • NIDDK NIH HHS - R01 DK105393()

Ligand and Target Discovery by Fragment-Based Screening in Human Cells.

  • Parker CG
  • Cell
  • 2017 Jan 26

Literature context:


Abstract:

Advances in the synthesis and screening of small-molecule libraries have accelerated the discovery of chemical probes for studying biological processes. Still, only a small fraction of the human proteome has chemical ligands. Here, we describe a platform that marries fragment-based ligand discovery with quantitative chemical proteomics to map thousands of reversible small molecule-protein interactions directly in human cells, many of which can be site-specifically determined. We show that fragment hits can be advanced to furnish selective ligands that affect the activity of proteins heretofore lacking chemical probes. We further combine fragment-based chemical proteomics with phenotypic screening to identify small molecules that promote adipocyte differentiation by engaging the poorly characterized membrane protein PGRMC2. Fragment-based screening in human cells thus provides an extensive proteome-wide map of protein ligandability and facilitates the coordinated discovery of bioactive small molecules and their molecular targets.

Funding information:
  • NCI NIH HHS - R01 CA132630()
  • NIDDK NIH HHS - R24 DK099810()
  • NIH HHS - S10 OD016357()