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GSE12421
Mus musculus
13 Downloadable Samples
Description
OBF1, also known as Bob.1 or OCA-B, is a B lymphocyte-specific transcription factor which coactivates Oct1 and Oct2 on B cell specific promoters. So far, the function of OBF1 has been mainly identified in late stage B cell populations. The central defect of OBF1 deficient mice is a severely reduced immune response to T cell-dependent antigens and a lack of germinal center formation in the spleen. Relatively little is known about a potential function of OBF1 in developing B cells. Here we have generated transgenic mice overexpressing OBF1 in B cells under the control of the immunoglobulin heavy chain promoter and enhancer. Surprisingly, these mice have greatly reduced numbers of follicular B cells in the periphery and have a compromised immune response. Furthermore, B cell differentiation is impaired at an early stage in the bone marrow. A first block is observed during B cell commitment and a second differentiation block is seen at the large preB2 cell stage. The cells that succeed to escape the block and to differentiate into mature B cells have post-translationally downregulated the expression of transgene, indicating that expression of OBF1 beyond the normal level early in B cell development is deleterious. Indeed ID3, which is a negative regulator of B cell differentiation, is upregulated in the EPLM and preB cells of the transgenic mice. Furthermore ID3 promoter contains an octamer site suggesting that it is a potential OBF-1 direct target gene. These results provide evidence that OBF1 expression has to be tightly regulated in early B cells to allow efficient B lymphocyte differentiation.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 31 Downloadable Samples
Description
Loss and heterozygosity for NDR1 predisposes mice to T-cell lymphoma development. To analyze mechanisms of tumor development in these mice chemically (ENU)-induced tumors were collected and RNA was extracted.
Publication Title
Ablation of the kinase NDR1 predisposes mice to the development of T cell lymphoma.
Sample Metadata Fields
Sex, Specimen part, Disease, Treatment
View Samples- Mus musculus
- 5 Downloadable Samples
Description
We have analyzed the transcript expression levels in Dicer knock-out embryonic stem (ES) cells 24 hours after transfection with either control siRNA agains Renilla luciferase or miRNA Mimics (Dharmacon) of mmu-miR-290 cluster members in order to identify primary targets of miR-290 cluster miRNAs.
Publication Title
MicroRNAs control de novo DNA methylation through regulation of transcriptional repressors in mouse embryonic stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Direct lineage conversion of adult mouse liver cells and B lymphocytes to neural stem cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
Description
The precise control of gene expression programs is critical for maintenance of cell state in emryonic stem cells. Cohesin has been shown to play an important role in maintaining gene expression programs by contributing to DNA loops between enhancers and promoters of active genes. The influence of condensin on gene expression is not well understood.
Publication Title
No associated publication
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 1 Downloadable Sample
Description
Increasing evidence suggests that Long non-coding RNAs (LncRNAs) represent a new class of regulators of stem cells. However, the roles of LncRNAs in stem cell maintenance and myogenesis remain largely unexamined. For this study, hundreds of novel intergenic LncRNAs were identified that are expressed in myoblasts and regulated during differentiation. One of these LncRNAs, termed LncMyoD, is encoded next to the Myod gene and is directly activated by MyoD during myoblast differentiation. Knockdown of LncMyoD strongly inhibits terminal muscle differentiation largely due to a failure to exit the cell cycle. LncMyoD directly binds to IGF2-mRNA-binding-protein 2 (IMP2) and negatively regulates IMP2-mediated translation of proliferation genes such as N-Ras and c-Myc. While the RNA sequence of LncMyoD is not well-conserved between human and mouse, its locus, gene structure and function is preserved. The MyoD-LncMyoD-IMP2 pathway elucidates a mechanism as to how MyoD blocks proliferation to create a permissive state for differentiation.
Publication Title
A long non-coding RNA, LncMyoD, regulates skeletal muscle differentiation by blocking IMP2-mediated mRNA translation.
Sample Metadata Fields
Age
View Samples- Mus musculus
- 4 Downloadable Samples
Description
The overexpression of transcription factors Oct4, Sox2, Klf4, and c-Myc reprograms a somatic nucleus to one that is transcriptionally and epigenetically indistinguishable from an embryonic stem (ES) cell. However, it is still unclear if transcription factors can completely convert the nucleus of a differentiated cell into that of a distantly related cell type such that it maintains complete transcriptional and epigenetic reprogramming in the absence of exogenous factor expression. To test this idea, we screened a library of doxycycline-inducible vectors encoding neural stem cell (NSC)-expressed genes and found that stable, self-maintaining NSC-like cells could be induced under defined growth conditions after transduction of transcription factors. These induced NSCs (iNSCs) were characterized in the absence of exogenous factor induction and were shown to be transcriptionally, epigenetically, and functionally similar to endogenous embryonic cortical NSCs. Importantly, iNSCs could be generated from multiple adult cell types including liver cells and B-cells with genetic rearrangements. Our results show that self-maintaining proliferative neural cells can be induced from non-ectodermal cells by expressing specific combinations of transcription factors.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 20 Downloadable Samples
Description
Mouse and human stem cells with features similar to those of embryonic stem cells have been derived from testicular cells. Although pluripotent stem cells have been obtained from defined germline stem cells (GSCs) of mouse neonatal testis, only multipotent stem cells have been obtained so far from defined cells of mouse adult testis. In this study we describe a robust and reproducible protocol for obtaining germline-derived pluripotent stem (gPS) cells from adult unipotent GSCs. Pluripotency of gPS cells was confirmed by in vitro and in vivo differentiation, including germ cell contribution and transmission. As determined by clonal analyses, gPS cells indeed originate from unipotent GSCs. We propose that the conversion process requires a GSC culture microenvironment that depends on the initial number of plated GSCs and the length of culture time.
Publication Title
Induction of pluripotency in adult unipotent germline stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 11 Downloadable Samples
Description
Reprogramming of somatic cells is a valuable tool to understand the mechanisms of regaining pluripotency and further opens up the possibility of generating patient-specific pluripotent stem cells. Reprogramming of mouse and human somatic cells into pluripotent stem cells, designated as induced pluripotent stem (iPS) cells, has been possible with the expression of the transcription factor quartet Oct4 (also known as Pou5f1), Sox2, c-Myc, and Klf4. Considering that ectopic expression of c-Myc causes tumourigenicity in offspring and retroviruses themselves can cause insertional mutagenesis, the generation of iPS cells with a minimal number of factors may hasten the clinical application of this approach. Here, we show that adult mouse neural stem cells express higher endogenous levels of Sox2 and c-Myc than embryonic stem cells, and that exogenous Oct4 together with either Klf4 or c-Myc are sufficient to generate iPS cells from neural stem cells. These two-factor (2F) iPS cells are similar to embryonic stem cells at the molecular level, contribute to development of the germ line, and form chimeras. We propose that, in inducing pluripotency, the number of reprogramming factors can be reduced when using somatic cells that endogenously express appropriate levels of complementing factors.
Publication Title
Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
Description
The four transcription factors Oct4, Sox2, Klf4, and c-Myc can induce pluripotency in mouse and human fibroblasts. We previously described direct reprogramming of adult mouse neural stem cells (NSCs) by Oct4 and either Klf4 or c-Myc. NSCs endogenously express Sox2, c-Myc, and Klf4 as well as several intermediate reprogramming markers. Here we report that exogenous expression of the germline-specific transcription factor Oct4 is sufficient to generate pluripotent stem cells from adult mouse NSCs. These one-factor induced pluripotent stem (1F iPS) cells are similar to embryonic stem cells in vitro and in vivo. Not only can these cells be efficiently differentiated into NSCs, cardiomyocytes and germ cells in vitro, but they are also capable of teratoma formation and germline transmission in vivo. Our results demonstrate that Oct4 is required and sufficient to directly reprogram NSCs to pluripotency.
Publication Title
Oct4-induced pluripotency in adult neural stem cells.
Sample Metadata Fields
No sample metadata fields
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