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GSE13690
Mus musculus
38 Downloadable Samples
Description
The genetic programs that promote retention of self-renewing leukemia stem cells (LSCs) at the apex of cellular hierarchies in acute myeloid leukemia (AML) are not known. In a mouse model of human AML, LSCs exhibit variable frequencies that correlate with the initiating MLL oncogene and are maintained in a self-renewing state by a transcriptional sub-program more akin to that of embryonic stem cells (ESCs) than adult stem cells. The transcription/chromatin regulatory factors Myb, Hmgb3 and Cbx5 are critical components of the program and suffice for Hoxa/Meis-independent immortalization of myeloid progenitors when co-expressed, establishing the cooperative and essential role of an ESC-like LSC maintenance program ancillary to the leukemia initiating MLL/Hox/Meis program. Enriched expression of LSC maintenance and ESC-like program genes in normal myeloid progenitors and poor prognosis human malignancies links the frequency of aberrantly self-renewing progenitor-like cancer stem cells to prognosis in human cancer.
Publication Title
Hierarchical maintenance of MLL myeloid leukemia stem cells employs a transcriptional program shared with embryonic rather than adult stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
Description
Normal myeloid lineage cell populations (C57BL/6 mice, aged 4-10 weeks, male or female) with three distinct immunophenotypes were prospectively isolated and characterized. In preparation for FACS sorting, bone marrow cells were separated into c-kit+ and c-kit- fractions using an AutoMACS device. C-kit+ cells were further fractionated based on Gr1 and Mac1 expression, and absence of lineage antigen expression (B220, TER119, CD3, CD4, CD8 and IL7R), by cell sorting. C-kit+ Gr1+ Mac1lo/- and c-kit+ Gr1+ Mac1+ displayed cytologic features of undifferentiated hematopoietic cells or myeloblasts, whereas c-kit- Gr1+ Mac1+ cells were mature neutrophils.
Publication Title
Hierarchical maintenance of MLL myeloid leukemia stem cells employs a transcriptional program shared with embryonic rather than adult stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
Description
Leukemia cells from mice with MLL-AF10 AML were fractionated into separate sub-populations on the basis of c-kit expression, which correlates with MLL LSC frequency (Somervaille and Cleary, 2006). The sorted AML sub-populations exhibited substantial differences in their frequencies of AML CFCs/LSCs (mean 14-fold) and morphologic features, consistent with a leukemia cell hierarchy with maturation through to terminally differentiated neutrophils.
Publication Title
Hierarchical maintenance of MLL myeloid leukemia stem cells employs a transcriptional program shared with embryonic rather than adult stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 3 Downloadable Samples
Description
Ccnyl1 is a newly identified genes, but the founction of which remained unclear, here we used the Ccnyl1 knockout mice to finding clues for its functional roles
Publication Title
CCNYL1, but Not CCNY, Cooperates with CDK16 to Regulate Spermatogenesis in Mouse.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 5 Downloadable Samples
Description
Several studies have shown that bone mineral density (BMD), a clinically measurable predictor of osteoporotic fracture, is the sum of genetic and environmental influences. In addition, serum IGF-1 levels have been correlated to both BMD and fracture risk. We previously identified a Quantitative Trait Locus (QTL) for Bone Mineral Density (BMD) on mouse Chromosome (Chr) 6 that overlaps a QTL for serum IGF-1. The B6.C3H-6T (6T) congenic mouse is homozygous for C57BL/6J (B6) alleles across the genome except for a 30 cM region on Chr 6 that is homozygous for C3H/HeJ (C3H) alleles. This mouse was created to study biology behind both the BMD and the serum IGF-1 QTLs and to identify the gene(s) underlying these QTLs. Female 6T mice have lower BMD and lower serum IGF-1 levels at all ages measured. As the liver is the major source of serum IGF-1, we examined differential expression in the livers of fasted female B6 and 6T mice by microarray.
Publication Title
A chromosomal inversion within a quantitative trait locus has a major effect on adipogenesis and osteoblastogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 14 Downloadable Samples
Description
The recent identification of cancer stem cells (CSCs) in multiple human cancers provides a new inroad to understanding tumorigenesis at the cellular level. CSCs are defined by their characteristics of self-renewal, multipotentiality, and tumor initiation upon transplantation. By testing for these defining characteristics, we provide evidence for the existence of CSCs in a transgenic mouse model of glioma, S100-verbB;Trp53. In this glioma model, CSCs are enriched in the side-population (SP) cells. These SP cells have enhanced tumor-initiating capacity, self-renewal, and multipotentiality compared to non-SP cells from the same tumors. Furthermore, gene expression analysis comparing FACS-sorted cancer SP cells to non-SP cancer cells and normal neural SP cells identified 45 candidate genes that are differentially expressed in glioma stem cells. We validated the expression of two genes from this list (S100a4 and S100a6) in primary mouse gliomas and human glioma samples. Analyses of xenografted human GBM (glioblatoma multiforme) cell lines and primary human glioma tissues show that S100A4 and S100A6 are expressed in a small subset of cancer cells and that their abundance is positively correlated to tumor grade. In conclusion, this study shows that CSCs exist in a mouse glioma model, suggesting that this model can be used to study the molecular and cellular characteristics of CSCs in vivo and to further test the cancer stem cell hypothesis.
Publication Title
Cancer stem cells are enriched in the side population cells in a mouse model of glioma.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 25 Downloadable Samples
Description
MicroRNAs have emerged as major genetic elements in the genesis and suppression of cancer. Here, multi-dimensional cancer genome analysis and validation has defined a novel Glioblastoma Multiforme (GBM) tumor suppressor pathway and mechanism of action centered on Quaking (QK), a member of the STAR family of RNA-binding proteins. Combined functional, biochemical and computational studies establish that p53 directly regulates QK gene expression, QK protein binds and stabilizes miR-20a of the cancer-relevant miR-17-92 cluster, and miR-20a in turn functions to regulate TGFR2 and the TGF signaling network. Linkage of these pathway components is supported by their genome and expression status across GBM specimens and by their gain- and loss-of-function interactions in in vitro and in vivo complementation studies. This p53-QK-miR-20a axis expands our understanding of the p53 tumor suppression network in cancer and reveals a novel tumor suppression mechanism involving regulation of specific cancer-relevant microRNAs.
Publication Title
STAR RNA-binding protein Quaking suppresses cancer via stabilization of specific miRNA.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
Description
Identify potential QK-regulated mRNAs and linked pathways by comparing the transcriptional profiles of shGFP- and shQK-transduced Ink4a/Arf-/- Pten-/- primary mouse astrocytes
Publication Title
STAR RNA-binding protein Quaking suppresses cancer via stabilization of specific miRNA.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
Description
Identify potential miR-20a regulated mRNAs and linked pathways in the setting of QK knockdown by comparing the transcriptional profiles of shQK-transduced primary mouse Ink4a/Arf-/- Pten-/- astrocytes together with miR-20a or a scrambled miRNA control (miR-NT)
Publication Title
STAR RNA-binding protein Quaking suppresses cancer via stabilization of specific miRNA.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 21 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Androgenetic haploid embryonic stem cells produce live transgenic mice.
Sample Metadata Fields
Specimen part, Cell line
View Samples