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GSE27686
Mus musculus
16 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Somatic stem cells mediate tissue maintenance for the lifetime of an organism. Despite the well-established longevity that is a prerequisite for such function, accumulating data argue for compromised stem cell function with age. Identifying the mechanisms underlying age-dependent stem cell dysfunction is therefore key to understand the aging process.
Publication Title
Accumulating mitochondrial DNA mutations drive premature hematopoietic aging phenotypes distinct from physiological stem cell aging.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The major myeloid blood cell lineages, including erythrocytes, platelets, granulocytes and macrophages, are generated from hematopoietic stem cells (HSC) by differentiation through a series of increasingly more committed progenitor cells. Precise phenotypic identification and functional characterization of such intermediate progenitors has important consequences for understanding fundamental differentiation processes and is clinically relevant since such events become dysregulated in various disease settings, including leukemia. While previous studies have suggested a hierarchy for myeloid differentiation involving a common progenitor through which all myeloid lineages are derived, several recent studies have suggested that such a developmental intermediate might not be an absolute requirement. Here, we evaluated the functional in vitro and in vivo potentials of a range of prospectively isolated myeloid precursors with differential expression of CD150, Endoglin and CD41. Our studies reveal a complex hierarchy of myeloerythroid progenitors with distinct and developmentally restricted lineage potentials. Global gene expression signatures of these cellular subsets revealed expression patterns consistent with their functional capacities, while hierarchical clustering analysis provides details on their lineage relationships. These data challenge existing models of hematopoietic differentiation, by suggesting that progenitors of the innate and adaptive immune system in the adult separate late, and to a large extent, following the divergence of megakaryocytic/erythroid potential.
Publication Title
Elucidation of the phenotypic, functional, and molecular topography of a myeloerythroid progenitor cell hierarchy.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Aging of hematopoietic stem cells (HSCs) leads to several functional changes, including alterations affecting self-renewal and differentiation. While it is well established that many of the age-induced changes are intrinsic to HSCs, less is known about the stability of this state. Here, we entertained the hypothesis that HSC aging is driven by the acquisition of permanent genetic mutations. To examine this issue at a functional level in vivo, we applied induced pluripotent stem (iPS) cell reprogramming of aged hematopoietic progenitors and allowed the resulting aged-derived iPS cells to reform hematopoiesis via blastocyst complementation. Next, we functionally characterized iPS-derived HSCs in primary chimeras and following the transplantation of 're-differentiated' HSCs into new hosts; the gold standard to assess HSC function. Our data demonstrate remarkably similar functional properties of iPS-derived and endogenous blastocyst-derived HSCs, despite the extensive chronological and proliferative age of the former. Our results therefore favor a model in which an underlying, but reversible, epigenetic component is a hallmark of HSC aging rather than being driven by an increased DNA mutation burden.
Publication Title
An epigenetic component of hematopoietic stem cell aging amenable to reprogramming into a young state.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
Illumina HiSeq 2000
Description
Genome wide RNA-seq from pGM and HSCs in response to expression of the MLL-ENL fusion gene Overall design: Examination of mRNA abundance in two cell types with or without induction of the MLL-ENL fusion gene (following 48h of culture)
Publication Title
Hematopoietic stem cells are intrinsically protected against MLL-ENL-mediated transformation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 134 Downloadable Samples
- Illumina HiSeq 2000
Description
We analysed the transcriptome of different HSC-enriched subpopulations of cells sorted from human umbilical cord blood and isolated from several individuals with different genetic backgrounds. We aim at identifying new cell surface markers associated with human HSC and downstream mature hematopoietic cell activity. Overall design: RNA-seq of CD34+CD45RA- cord blood cells from 17 non-pooled individuals.
Publication Title
GPR56 identifies primary human acute myeloid leukemia cells with high repopulating potential in vivo.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 121 Downloadable Samples
- Illumina HiSeq 2000
Description
The goal of the study was to identify genes that are directly or indirectly coregulated by the AhR pathway in primary human AML cells. Patient AML cells were treated for 16 hours with the two indirubin derivatives 6-bromoindirubin-3''oxime (BIO), 1-Methyl-6-bromoindirubin-3''oxime (MeBIO), the AHR-antagonist SR1 (StemReginin1), combinations of BIO+SR1 and MeBIO+SR1 or DMSO alone at indicated concentrations prior to RNA extraction for sequencing. Overall design: RNA-Seq performed on 5 primary AML samples fresh (t0) and after exposure to AhR-agonists (2), -antagonist (1), and DMSO Contributor: Leucegene Project, IRIC
Publication Title
GPR56 identifies primary human acute myeloid leukemia cells with high repopulating potential in vivo.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- IlluminaHiSeq2000
Description
In this study the gene expression in cells infected with lytic and non-lytic variants of coxsackievirus B2 Ohio (CVB2O) were analyzed using next generation sequencing. This approach was selected with the purpose of elucidating the effects of lytic and non-lytic viruses on host cell transcription. Total RNA was extracted from infected cells, next generation sequencing was performed, and the reads were subsequently mapped against the human and CVB2O genomes. The amount of intracellular virions was measured, showing a relative amount of virus RNA 13 times higher in the cells infected with the lytic variant, vVP1Q164K, compared to cells infected by the non-lytic CVB2Owt. Furthermore, differential gene expression in the cells infected with the two viruses was identified and a number of genes singled out as possible keys to the answer of how the viruses interact with the host cells, resulting in lytic or non-lytic infections. Overall design: 4 samples, two samples of one strain, one sample of a different strain, and one control sample
Publication Title
The Transcriptome of Rhabdomyosarcoma Cells Infected with Cytolytic and Non-Cytolytic Variants of Coxsackievirus B2 Ohio-1.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Using a mimic miR-200c was restored to an aggressive, Type 2 endometrial cancer cell line, Hec50
Publication Title
MicroRNA-200c mitigates invasiveness and restores sensitivity to microtubule-targeting chemotherapeutic agents.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
Piwi proteins and Piwi-interacting small RNAs (piRNAs) have known functions in transposon silencing in the male germline of fetal and newborn mice. Both are also necessary for spermatogenesis in adult testes, however, their function here remains a mystery. Here, we use germ cell isolations and small RNA sequencing to show that most piRNAs in meiotic spermatocytes originate from clusters in intergenic non-repeat regions of DNA. The regulation of these piRNA clusters, including the processing of the precursor transcripts into individual piRNAs, is accomplished through mostly unknown processes. We present evidence for a regulatory mechanism for one such cluster, named cluster 1082B, located on chromosome 7 in the mouse genome, containing 788 unique piRNAs. The precursor transcript and individual piRNAs within the cluster are repressed by the Alkbh1 dioxygenase and the transcription repressor Tzfp, which are believed to be interaction partners in testis. We observe more than a thousand-fold upregulation of individual piRNAs in pachytene spermatocytes isolated from Alkbh1-/- and TzfpGTi/GTi testes. Repression is further supported by the identification of a 10 bp Tzfp recognition sequence contained within the precursor transcript. Downregulation of long interspersed elements 1 (LINE1) and intracisternal A-particle (IAP) transcripts in the Alkbh1-/- and TzfpGTi/GTi testes leads us to propose a potential role for the 1082B-encoded piRNAs in transposon silencing. Overall design: Characterization of small RNAs in mouse pachytene spermatocytes for wild-type (WT) and Alkbh1-/- and TzfpGTi/GTi, and mRNA in mouse pachytene spermatocytes for wild-type (WT) and Alkbh1-/-
Publication Title
Alkbh1 and Tzfp repress a non-repeat piRNA cluster in pachytene spermatocytes.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Growth hormone signaling in hepatocytes is fundamentally important. Disruptions in this pathway have led to fatty liver and other metabolic abnormalities. Growth hormone signals through the JAK2/STAT5 pathway. Mice with hepatocyte specific deletion of STAT5 were previously shown to develop fatty liver. Our aim in this study was to determine the effect of deleting JAK2 in hepatocytes on liver gene expression. To do so, we generated animals with hepatocyte specific deletion of JAK2.
Publication Title
Abrogation of growth hormone secretion rescues fatty liver in mice with hepatocyte-specific deletion of JAK2.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples