Transcriptome data of WT and Ddb1-KO activated CD4+ T cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE176437 | GEO | 2021/08/19
REPOSITORIES: GEO
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Project description:Transcriptome data of WT and Ddb1-KO activated CD4+ T cells
| PRJNA736248 | ENA
Project description:Purpose: Next-generation sequencing (NGS) to reveal CIC target genes in CD4 T cells. The goals of this study are to compare NGS-derived CD4 T cell transcriptome in the presence or absence of CIC.
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Project description:Quiescent hepatic stem cells (HSCs) can be activated when hepatocyte proliferation is compromised. Chemical injury rodent models have been widely used to study the locazation, biomarkers, and signaling pathways in HSCs, but these models usually exhibit severe promiscuous toxicity and fail to distinguish damaged and non-damaged cells. Our goal is to establish new animal models to overcome these limitations, thereby providing new insights into HSC biology and application. We generated mutant mice with constitutive or inducible deletion of Damaged DNA Binding protein 1 (DDB1), an E3 ubiquitin ligase, in hepatocytes. We show that deletion of DDB1 abolishes self-renewal capacity of mouse hepatocytes in vivo, leading to compensatory activation and proliferation of DDB1-expressing OCs. Importantly, the DDB1 mutant mice exhibit very minor liver damage, compared to a chemical injury model. Microarray analysis reveals several previously unrecognized markers, enriched in oval cells. This genetic model in which irreversible inhibition of hepatocyte duplication results in HSC-driven liver regeneration. The DDB1 mutant mice can be broadly applied to studies of HSC differentiation, HSC niche and HSCs as origin of liver cancer. Total RNA obtained from isolated EpCAM+ cells from DDB1 mutant mice compared to wild type hepatocytes
2012-01-01 | E-GEOD-31588 | biostudies-arrayexpress
Project description:Hematopoietic stem cells (HSC) are regulated to keep the balance between self-renewal and differentiation. However, little is known about post-translational regulations in HSCs. In this study, we characterize the role of DDB1, a component of the Cul4A-DDB1 E3 ubiquitin ligase complex, in HSCs and progenitors by using conditional DDB1 knockout models. We show that the maintenance and differentiation of both adult and fetal HSCs and progenitor cells is dependent on DDB1 function. Deletion of DDB1 alters cell cycle progression and induces apoptosis. Furthermore, deletion of DDB1 in developing thymocytes had no effects on T cell differentiation, whereas DDB1-deficient peripheral T cells were not able to enter cell cycle when stimulated in vitro. In addition, DDB1 is essential for T cell leukemia initiation. Our results reveal that DDB1 is required for adult and fetal hematopoiesis as it controls progenitor and stem cell homeostasis. Transcriptional consequences of inactivating DDB1 in fetal LSK cells. Four samples were analyzed: wild-type (WT) control and DDB1-deficient (DDB1) Lin-ckit+Sca1+ (LSK) cells sorted from fetal livers E16.5 of DDB1 flox/flox, VavCre+ and control mice.
2015-07-10 | E-GEOD-70658 | biostudies-arrayexpress
Project description:Adipose tissues play a pivotal role in energy homeostasis. They are existent in two forms: white adipose tissue and brown adipose tissue (BAT). Being the primary source of non-shivering thermogenesis of mammals, BAT plays an irreplaceable role in maintaining body temperature . Damaged DNA binding protein 1 (DDB1) is usually recognized as a component of the CUL4-DDB1 E3 complex. We have previously shown that DDB1 functions independently of CUL4 to promote adipogenesis. In the thesis, we focus on the function of DDB1 in mature adipocytes. We crossed Ddb1f/f mice with Adipoq-Cre or Ucp1-Cre mice to generate adipose tissue or BAT-specific mice, designated Ddb1-AKO and Ddb1-BKO mice respectively. At 8-12 weeks, BAT in these mice was servely whitened with decreased mitochdiral content. The thermogenic genes were also significantly downregulated at both RNA and protein levels. To further characterize the effect of DDB1 on thermogenesis, we first examined the bdy temperature of the pulps on postnatal day 3, and found that depletion of DDB1 caused a significant decrease in surface temperature.When the adult mice were subjected to cold challenge, both Ddb1-AKO and Ddb1-BKO mice showed dramatically decreased body temperature compared with control mice. At the end of the experiment, Ddb1-AKO and Ddb1-BKO mice had higher contents in BAT triglycerides and lower blood glucose level. Furthermore, the oxygen comsumption in Ddb1-AKO and Ddb1-BKO mice failed to respond to epinephrine injection. . All these results above demonstrated that lacking of DDB1 in brown adipocytes leads to a destruction in thermogenesis of BAT. We have also examined the phenotypes of Ddb1-AKO and Ddb1-BKO mice on high-fat-diet feeding. Compared with control mice, these mice showed decreased body weight, but significantly glucose intolerance and increased triglycierde content in liver, indicating that these mice have partial lipodystrophy. To study whether the effect of DDB1 was dependent on CUL4, we generated adipose tissue-specific Cul4a or CUl4b knockout mice, and found that these mice have no visible defect in BAT morphology compared with control mice, indicating a CUL4-independent function of DDB1. RNA-Seq analysis revealed that DDB1 is required for cold-induced expression of around 900 genes. ChIP-Seq analysis revelaed that these genes were subjected to regulation of promoter-proximally paused RNA polymerase II (Pol II), and that DDB1 is required for the release of paused Pol II upon cold stimulation. Our findings have thus revealed that DDB1 plays an important role in maintaining the theremogenic function of BAT by regulating the expression of thermogenic genes upon cold stimulation. Our studies will shed insights into transcriptional regulation of thermogenic gene
2024-12-21 | GSE192466 | GEO
Project description:Adipose tissues play a pivotal role in energy homeostasis. They are existent in two forms: white adipose tissue and brown adipose tissue (BAT). Being the primary source of non-shivering thermogenesis of mammals, BAT plays an irreplaceable role in maintaining body temperature . Damaged DNA binding protein 1 (DDB1) is usually recognized as a component of the CUL4-DDB1 E3 complex. We have previously shown that DDB1 functions independently of CUL4 to promote adipogenesis. In the thesis, we focus on the function of DDB1 in mature adipocytes. We crossed Ddb1f/f mice with Adipoq-Cre or Ucp1-Cre mice to generate adipose tissue or BAT-specific mice, designated Ddb1-AKO and Ddb1-BKO mice respectively. At 8-12 weeks, BAT in these mice was servely whitened with decreased mitochdiral content. The thermogenic genes were also significantly downregulated at both RNA and protein levels. To further characterize the effect of DDB1 on thermogenesis, we first examined the bdy temperature of the pulps on postnatal day 3, and found that depletion of DDB1 caused a significant decrease in surface temperature.When the adult mice were subjected to cold challenge, both Ddb1-AKO and Ddb1-BKO mice showed dramatically decreased body temperature compared with control mice. At the end of the experiment, Ddb1-AKO and Ddb1-BKO mice had higher contents in BAT triglycerides and lower blood glucose level. Furthermore, the oxygen comsumption in Ddb1-AKO and Ddb1-BKO mice failed to respond to epinephrine injection. . All these results above demonstrated that lacking of DDB1 in brown adipocytes leads to a destruction in thermogenesis of BAT. We have also examined the phenotypes of Ddb1-AKO and Ddb1-BKO mice on high-fat-diet feeding. Compared with control mice, these mice showed decreased body weight, but significantly glucose intolerance and increased triglycierde content in liver, indicating that these mice have partial lipodystrophy. To study whether the effect of DDB1 was dependent on CUL4, we generated adipose tissue-specific Cul4a or CUl4b knockout mice, and found that these mice have no visible defect in BAT morphology compared with control mice, indicating a CUL4-independent function of DDB1. RNA-Seq analysis revealed that DDB1 is required for cold-induced expression of around 900 genes. ChIP-Seq analysis revelaed that these genes were subjected to regulation of promoter-proximally paused RNA polymerase II (Pol II), and that DDB1 is required for the release of paused Pol II upon cold stimulation. Our findings have thus revealed that DDB1 plays an important role in maintaining the theremogenic function of BAT by regulating the expression of thermogenic genes upon cold stimulation. Our studies will shed insights into transcriptional regulation of thermogenic gene
2024-12-21 | GSE192457 | GEO
Project description:Quiescent hepatic stem cells (HSCs) can be activated when hepatocyte proliferation is compromised. Chemical injury rodent models have been widely used to study the locazation, biomarkers, and signaling pathways in HSCs, but these models usually exhibit severe promiscuous toxicity and fail to distinguish damaged and non-damaged cells. Our goal is to establish new animal models to overcome these limitations, thereby providing new insights into HSC biology and application. We generated mutant mice with constitutive or inducible deletion of Damaged DNA Binding protein 1 (DDB1), an E3 ubiquitin ligase, in hepatocytes. We show that deletion of DDB1 abolishes self-renewal capacity of mouse hepatocytes in vivo, leading to compensatory activation and proliferation of DDB1-expressing OCs. Importantly, the DDB1 mutant mice exhibit very minor liver damage, compared to a chemical injury model. Microarray analysis reveals several previously unrecognized markers, enriched in oval cells. This genetic model in which irreversible inhibition of hepatocyte duplication results in HSC-driven liver regeneration. The DDB1 mutant mice can be broadly applied to studies of HSC differentiation, HSC niche and HSCs as origin of liver cancer.
2012-01-01 | GSE31588 | GEO
Project description:Hematopoietic stem cells (HSC) are regulated to keep the balance between self-renewal and differentiation. However, little is known about post-translational regulations in HSCs. In this study, we characterize the role of DDB1, a component of the Cul4A-DDB1 E3 ubiquitin ligase complex, in HSCs and progenitors by using conditional DDB1 knockout models. We show that the maintenance and differentiation of both adult and fetal HSCs and progenitor cells is dependent on DDB1 function. Deletion of DDB1 alters cell cycle progression and induces apoptosis. Furthermore, deletion of DDB1 in developing thymocytes had no effects on T cell differentiation, whereas DDB1-deficient peripheral T cells were not able to enter cell cycle when stimulated in vitro. In addition, DDB1 is essential for T cell leukemia initiation. Our results reveal that DDB1 is required for adult and fetal hematopoiesis as it controls progenitor and stem cell homeostasis. Transcriptional consequences of inactivating DDB1 in fetal LSK cells.
2015-07-10 | GSE70658 | GEO
Project description:DDB1 is typically recognized as a component of the Cullin4 (CUL4)-RING E3 ubiquitin ligase complex. Here, we show that DDB1 functions independently of CUL4 to promote adipogenesis and diet-induced obesity. In contrast to depletion of CUL4A or CUL4B that stimulates adipogenesis, lack of DDB1 dramatically suppresses the process. Re-introduction of a DDB1 mutant that lacks the binding ability to CUL4A or CUL4B fully restores adipogenesis in DDB1-deficient preadipocytes. Furthermore, while inducibly knocking out Cul4a or Cul4b in mice aggravates diet-induced obesity, Ddb1+/- mice are lean on high-fat diet. Mechanistically, by binding the bromodomain-containing histone reader BRWD3, DDB1 is recruited to acetylated histones in the proximal promoters of immediate-early response genes, where it facilitates the release of paused RNA polymerase II (Pol II) and activates the transcription of these genes. Our findings have thus uncovered a mechanism of activating the transcriptional cascade in adipogenesis by DDB1-mediated release of paused Pol II.
2023-09-17 | GSE158172 | GEO
Project description:DDB1 is typically recognized as a component of the Cullin4 (CUL4)-RING E3 ubiquitin ligase complex. Here, we show that DDB1 functions independently of CUL4 to promote adipogenesis and diet-induced obesity. In contrast to depletion of CUL4A or CUL4B that stimulates adipogenesis, lack of DDB1 dramatically suppresses the process. Re-introduction of a DDB1 mutant that lacks the binding ability to CUL4A or CUL4B fully restores adipogenesis in DDB1-deficient preadipocytes. Furthermore, while inducibly knocking out Cul4a or Cul4b in mice aggravates diet-induced obesity, Ddb1+/- mice are lean on high-fat diet. Mechanistically, by binding the bromodomain-containing histone reader BRWD3, DDB1 is recruited to acetylated histones in the proximal promoters of immediate-early response genes, where it facilitates the release of paused RNA polymerase II (Pol II) and activates the transcription of these genes. Our findings have thus uncovered a mechanism of activating the transcriptional cascade in adipogenesis by DDB1-mediated release of paused Pol II.
2023-09-17 | GSE158171 | GEO