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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Let-7 represses Nr6a1 and a mid-gestation developmental program in adult fibroblasts [ChIP-seq_histone]

ABSTRACT: MicroRNAs (miRNAs) are critical to proliferation, differentiation, and development. Here, we characterize gene expression in murine Dicer-null adult mesenchymal stem cell lines, a fibroblast cell type. Loss of Dicer leads to de-repression of let-7 targets at levels that exceed 10-100 fold with increases in transcription. Direct and indirect targets of this miRNA belong to a mid-gestation embryonic program that encompasses known oncofetal genes as well as oncogenes not previously associated with an embryonic state. Surprisingly, this mid-gestation program represents a distinct period that occurs between the pluripotent state of the inner cell mass at embryonic day 3.5 and the induction of let-7, upon differentiation, at embryonic day 10.5. Within this mid-gestation program, we characterize the let-7 target Nr6a1, an embryonic transcriptional repressor that regulates gene expression in adult fibroblasts following miRNA loss. In total, let-7 is required for the continual suppression of embryonic gene expression in adult cells, a mechanism that may underlie its tumor suppressive function. Examination of histone modifications in adult mesenchymal stem cells (immortalized monoclonal lines of murine MSCs) with and without Dicer (WT: Dicer f/f, KO: Dicer -/-).

ORGANISM(S): Mus musculus

SUBMITTER: A Bhutkar

PROVIDER: E-GEOD-44159 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Let-7 represses Nr6a1 and a mid-gestation developmental program in adult fibroblasts [ChIP-seq_nr6a1]

Project description:MicroRNAs (miRNAs) are critical to proliferation, differentiation, and development. Here, we characterize gene expression in murine Dicer-null adult mesenchymal stem cell lines, a fibroblast cell type. Loss of Dicer leads to de-repression of let-7 targets at levels that exceed 10-100 fold with increases in transcription. Direct and indirect targets of this miRNA belong to a mid-gestation embryonic program that encompasses known oncofetal genes as well as oncogenes not previously associated with an embryonic state. Surprisingly, this mid-gestation program represents a distinct period that occurs between the pluripotent state of the inner cell mass at embryonic day 3.5 and the induction of let-7, upon differentiation, at embryonic day 10.5. Within this mid-gestation program, we characterize the let-7 target Nr6a1, an embryonic transcriptional repressor that regulates gene expression in adult fibroblasts following miRNA loss. In total, let-7 is required for the continual suppression of embryonic gene expression in adult cells, a mechanism that may underlie its tumor suppressive function. Examination of genes directly bound by Flag-HA-NR6A1 in Dicer WT (Dicer f/f) adult mesenchymal stem cells (immortalized monoclonal lines of murine MSCs).

2013-04-10 | E-GEOD-44160 | biostudies-arrayexpress

Let-7 represses Nr6a1 and a mid-gestation developmental program in adult fibroblasts [mRNA-seq_Flag-HA-NR6A1_overexpr]

Project description:MicroRNAs (miRNAs) are critical to proliferation, differentiation, and development. Here, we characterize gene expression in murine Dicer-null adult mesenchymal stem cell lines, a fibroblast cell type. Loss of Dicer leads to de-repression of let-7 targets at levels that exceed 10-100 fold with increases in transcription. Direct and indirect targets of this miRNA belong to a mid-gestation embryonic program that encompasses known oncofetal genes as well as oncogenes not previously associated with an embryonic state. Surprisingly, this mid-gestation program represents a distinct period that occurs between the pluripotent state of the inner cell mass at embryonic day 3.5 and the induction of let-7, upon differentiation, at embryonic day 10.5. Within this mid-gestation program, we characterize the let-7 target Nr6a1, an embryonic transcriptional repressor that regulates gene expression in adult fibroblasts following miRNA loss. In total, let-7 is required for the continual suppression of embryonic gene expression in adult cells, a mechanism that may underlie its tumor suppressive function. mRNAs from Flag-HA-NR6A1-overexpressing Dicer wild-type adult mesenchymal stem cells (immortalized monoclonal lines of murine MSCs) and vector-only Dicer WT MSCs were analyzed.

2013-04-10 | E-GEOD-44158 | biostudies-arrayexpress

Let-7 represses Nr6a1 and a mid-gestation developmental program in adult fibroblasts [3p arrays]

Project description:MicroRNAs (miRNAs) are critical to proliferation, differentiation, and development. Here, we characterize gene expression in murine Dicer-null adult mesenchymal stem cell lines, a fibroblast cell type. Loss of Dicer leads to de-repression of let-7 targets at levels that exceed 10-100 fold with increases in transcription. Direct and indirect targets of this miRNA belong to a mid-gestation embryonic program that encompasses known oncofetal genes as well as oncogenes not previously associated with an embryonic state. Surprisingly, this mid-gestation program represents a distinct period that occurs between the pluripotent state of the inner cell mass at embryonic day 3.5 and the induction of let-7, upon differentiation, at embryonic day 10.5. Within this mid-gestation program, we characterize the let-7 target Nr6a1, an embryonic transcriptional repressor that regulates gene expression in adult fibroblasts following miRNA loss. In total, let-7 is required for the continual suppression of embryonic gene expression in adult cells, a mechanism that may underlie its tumor suppressive function. Three dicer heterozygotes and 3 dicer null sarcoma cell lines.

2013-04-10 | E-GEOD-44162 | biostudies-arrayexpress

Let-7 represses Nr6a1 and a mid-gestation developmental program in adult fibroblasts [RNA-seq_siRNA_transfection]

Project description:MicroRNAs (miRNAs) are critical to proliferation, differentiation, and development. Here, we characterize gene expression in murine Dicer-null adult mesenchymal stem cell lines, a fibroblast cell type. Loss of Dicer leads to de-repression of let-7 targets at levels that exceed 10-100 fold with increases in transcription. Direct and indirect targets of this miRNA belong to a mid-gestation embryonic program that encompasses known oncofetal genes as well as oncogenes not previously associated with an embryonic state. Surprisingly, this mid-gestation program represents a distinct period that occurs between the pluripotent state of the inner cell mass at embryonic day 3.5 and the induction of let-7, upon differentiation, at embryonic day 10.5. Within this mid-gestation program, we characterize the let-7 target Nr6a1, an embryonic transcriptional repressor that regulates gene expression in adult fibroblasts following miRNA loss. In total, let-7 is required for the continual suppression of embryonic gene expression in adult cells, a mechanism that may underlie its tumor suppressive function. mRNAs from adult mesenchymal stem cells (immortalized monoclonal lines of murine MSCs) with and without Dicer (WT: Dicer f/f, KO: Dicer -/-), were analyzed. WT and KO cells were transfected with a nontargeting control siRNA. KO cells were separately transfected with a synthetic let-7g siRNA duplex, or an siRNA targeting Nr6a1.

2013-04-10 | E-GEOD-44157 | biostudies-arrayexpress

Let-7 represses Nr6a1 and a mid-gestation developmental program in adult fibroblasts [small_RNA-Seq]

Project description:MicroRNAs (miRNAs) are critical to proliferation, differentiation, and development. Here, we characterize gene expression in murine Dicer-null adult mesenchymal stem cell lines, a fibroblast cell type. Loss of Dicer leads to de-repression of let-7 targets at levels that exceed 10-100 fold with increases in transcription. Direct and indirect targets of this miRNA belong to a mid-gestation embryonic program that encompasses known oncofetal genes as well as oncogenes not previously associated with an embryonic state. Surprisingly, this mid-gestation program represents a distinct period that occurs between the pluripotent state of the inner cell mass at embryonic day 3.5 and the induction of let-7, upon differentiation, at embryonic day 10.5. Within this mid-gestation program, we characterize the let-7 target Nr6a1, an embryonic transcriptional repressor that regulates gene expression in adult fibroblasts following miRNA loss. In total, let-7 is required for the continual suppression of embryonic gene expression in adult cells, a mechanism that may underlie its tumor suppressive function. Small RNAs from adult mesenchymal stem cells (immortalized clonal lines of murine MSCs) with and without Dicer (Dicer f/f, Dicer -/-) were analyzed.

2013-04-10 | E-GEOD-44156 | biostudies-arrayexpress

Let-7 represses Nr6a1 and a mid-gestation developmental program in adult fibroblasts [CLIP-Seq]

Project description:MicroRNAs (miRNAs) are critical to proliferation, differentiation, and development. Here, we characterize gene expression in murine Dicer-null adult mesenchymal stem cell lines, a fibroblast cell type. Loss of Dicer leads to de-repression of let-7 targets at levels that exceed 10-100 fold with increases in transcription. Direct and indirect targets of this miRNA belong to a mid-gestation embryonic program that encompasses known oncofetal genes as well as oncogenes not previously associated with an embryonic state. Surprisingly, this mid-gestation program represents a distinct period that occurs between the pluripotent state of the inner cell mass at embryonic day 3.5 and the induction of let-7, upon differentiation, at embryonic day 10.5. Within this mid-gestation program, we characterize the let-7 target Nr6a1, an embryonic transcriptional repressor that regulates gene expression in adult fibroblasts following miRNA loss. In total, let-7 is required for the continual suppression of embryonic gene expression in adult cells, a mechanism that may underlie its tumor suppressive function. Adult mesenchymal stem cells (immortalized monoclonal lines of murine MSCs) with Dicer (WT: Dicer f/f), were infected with dox-inducible Flag-HA-hAgo2 or untagged hAgo2 and then UV cross-linked. An immunoprecipitation was carried out with anti-Flag and anti-HA antibodies, and associated RNAs were sequenced.

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Let-7 represses Nr6a1 and a mid-gestation developmental program in adult fibroblasts [Exon array]

Project description:MicroRNAs (miRNAs) are critical to proliferation, differentiation, and development. Here, we characterize gene expression in murine Dicer-null adult mesenchymal stem cell lines, a fibroblast cell type. Loss of Dicer leads to de-repression of let-7 targets at levels that exceed 10-100 fold with increases in transcription. Direct and indirect targets of this miRNA belong to a mid-gestation embryonic program that encompasses known oncofetal genes as well as oncogenes not previously associated with an embryonic state. Surprisingly, this mid-gestation program represents a distinct period that occurs between the pluripotent state of the inner cell mass at embryonic day 3.5 and the induction of let-7, upon differentiation, at embryonic day 10.5. Within this mid-gestation program, we characterize the let-7 target Nr6a1, an embryonic transcriptional repressor that regulates gene expression in adult fibroblasts following miRNA loss. In total, let-7 is required for the continual suppression of embryonic gene expression in adult cells, a mechanism that may underlie its tumor suppressive function. 2 monoclonal mesenchymal cell lines (clones 6 and 12) with Dicer and 4 derivative clones (6.8, 6.9, 12.2 and 12.4) lacking Dicer, all passaged under normal, untreated culture conditions.

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Let-7 represses Nr6a1 and a mid-gestation developmental program in adult fibroblasts [mRNA-seq_Flag-HA-NR6A1_overexpr]

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