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SRP162235
Mus musculus
14 Downloadable Samples
Illumina HiSeq 2500
Description
Adult hematopoiesis has been studied in terms of progenitor differentiation potentials, whereas its kinetics in vivo is poorly understood. We combined inducible lineage tracing of endogenous adult hematopoietic stem cells (HSC) with flow cytometry and single-cell RNA sequencing to characterize early steps of hematopoietic differentiation in the steady state. Labeled cells, comprising primarily long-term HSC and some short-term HSC, produced megakaryocytic lineage progeny within one week, in a process that required only 2-3 cell divisions. Erythroid and myeloid progeny emerged simultaneously by 2 weeks, and included a progenitor population with expression features of both lineages. Myeloid progenitors at this stage showed diversification into granulocytic, monocytic and dendritic cell types, and rare intermediate cell states could be detected. In contrast, lymphoid differentiation was virtually absent within the first 3 weeks of tracing. These results show that continuous differentiation of HSC rapidly produces major hematopoietic lineages and cell types, and reveal fundamental kinetic differences between megakaryocytic, erythroid, myeloid and lymphoid differentiation. Overall design: We combined inducible lineage tracing of endogenous adult hematopoietic stem cells (HSC) with flow cytometry and single-cell RNA sequencing to characterize early steps of hematopoietic differentiation in the steady state.
Publication Title
Kinetics of adult hematopoietic stem cell differentiation in vivo.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 3 Downloadable Samples
- Illumina HiSeq 2500
Description
Hematopoietic stem cells (HSC) sustain long-term reconstitution of hematopoiesis in primary transplantation recipients. Few HSC can serially reconstitute secondary recipients, and their identity and contribution to normal hematopoiesis remain moot. We directed transgene expression to a distinct fraction of HSC in the adult bone marrow. Epxression of the reporter transgene segregated with reconstituting activity during secondary transplantations. The labeled cells had an undifferentiated phenotype and expression profile, were slow-cycling and localized to the vascular niche. Inducible genetic labeling showed the transgene-expressing HSC gave rise to other cells within the HSC populations, confirming their top position in the differentiation hierarchy. Importantly, labeled HSC gave rise to more than two-thirds of all myeloid cells and platelets in adult mice, and this contribution could be further accelerated by interferon response. Thus, the rare "top-level" HSC with serial reconstitution capacity also serve as the major source of endogenous hematopoiesis in adult animals. Overall design: Sorted LSK CD48- CD150+ Map17-GFP+ and Map17-GFP- HSCs and LSK CD48+ CD150- Map17-GFP-MPPs were sequenced for mRNA profiling.
Publication Title
Hematopoietic Stem Cells Are the Major Source of Multilineage Hematopoiesis in Adult Animals.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
To determine if RU-486 would be effective as a chemopreventive agent, microarrays were used to analyse global gene expression changes in wild-type vs. MMTV-PAX8PPARg mice to determine their differential response to RU486
Publication Title
The chemopreventive effect of mifepristone on mammary tumorigenesis is associated with an anti-invasive and anti-inflammatory gene signature.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
The role of Sca-1 on mammary tumorigenesis was assessed. Microarrays were used to analyse global gene expression changes in Sca-1 KO mice versus wild-type mice and determine the differential responses to MP and DMBA-induced Mammary carcinogenesis
Publication Title
Stem cell antigen-1 deficiency enhances the chemopreventive effect of peroxisome proliferator-activated receptorγ activation.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Expression data from this experiment is part of a larger project aimed at defining the individual effects and synergistic effects of ROCK inhibitor Y-27632 and conditioned media from irradiated J2 cells when applied to epithelial cells. This data set consists of four individual samples, each of which are total RNA collected from human foreskin keratinocyte cells, either grown in F medium (control), treated with Y-27632, grown in conditioned medium (as described in associated publication), or both treatments.
Publication Title
Multifactorial analysis of conditional reprogramming of human keratinocytes.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 35 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Cancer cells interact with surrounding stromal fibroblasts during tumorigenesis, but the complex molecular rules that govern these interactions remain poorly understood, thus hindering the development of therapeutic strategies to target cancer stroma. We have taken a mathematical approach to begin defining these rules by performing large-scale quantitative analysis of fibroblast effects on cancer cell proliferation across more than four hundred heterotypic cell line pairings. Systems-level modeling of this complex dataset using singular value decomposition revealed that normal tissue fibroblasts variably express at least two functionally distinct activities, one which reflects transcriptional programs associated with activated mesenchyme, that act either coordinately or at cross-purposes to modulate cancer cell proliferation. To gain insight into the molecular identity of these fibroblast activities, we isolated RNA from 36 human skin and lung fibroblast cell line monocultures from Coriell Repositories or ATCC and performed microarray-based gene expression profiling using Affymetrix gene chips.
Publication Title
Systems-level modeling of cancer-fibroblast interaction.
Sample Metadata Fields
Sex, Age, Race
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
The role of murine peroxisome proliferator-activated receptor-delta (PPARd) in mammary tumorigenesis was assessed. Microarrays were used to analyse global gene expression to determine changes in MMTV-PPARd transgenic mice versus wild-type mice and the effect of GW501516.
Publication Title
PPARδ induces estrogen receptor-positive mammary neoplasia through an inflammatory and metabolic phenotype linked to mTOR activation.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Germline stem cell self-renewal and differentiation are required for sustained production of gamates. GSC differentiation in drosophila requires expression of setdb1 by the somatic niche, however its function is not known.
Publication Title
Transposon Dysregulation Modulates dWnt4 Signaling to Control Germline Stem Cell Differentiation in Drosophila.
Sample Metadata Fields
Specimen part
View Samples- Caenorhabditis elegans
- 9 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Hemes are essential but potentially cytotoxic cofactors that participate in critical and diverse biological processes. Although the pathway and intermediates for heme biosynthesis have been well defined, the intracellular networks which mediate heme trafficking remain unknown. Caenorhabditis elegans and related helminths are natural heme auxotrophs requiring environmental heme for growth and development. We exploited this auxotrophy to identify HRG-1 and HRG-4 in C. elegans and show that they are essential for heme homeostasis and normal vertebrate development. We demonstrate that heme deficiency upregulates expression of hrg-4 and its evolutionarily conserved paralog hrg-1. Depletion of either HRG-1 or HRG-4 in worms results in disruption of organismal heme sensing and abnormal response to heme analogs. HRG-1 and HRG-4 are novel transmembrane proteins that bind heme and have evolutionarily conserved functions. Transient knockdown of hrg-1 in zebrafish leads to hydrocephalus, yolk tube malformations, and, most strikingly, profound defects in erythropoiesis - phenotypes that are fully rescued by worm HRG-1. These findings reveal unanticipated and conserved pathways for cellular heme trafficking in animals that defines the paradigm for eukaryotic heme transport. Uncovering the mechanisms of heme transport in C. elegans will provide novel insights into human disorders of heme metabolism and generate unique anthelmintics to combat worm infestations.
Publication Title
Haem homeostasis is regulated by the conserved and concerted functions of HRG-1 proteins.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies.
Sample Metadata Fields
Cell line, Treatment
View Samples