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GSE8407
Mus musculus
15 Downloadable Samples
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
- 1 Downloadable Sample
Description
Gene expression profiling using microarray has been limited to profiling of differentially expressed genes at comparison setting since probesets for different genes have different sensitivities. We overcome this limitation by using a very large number of varied microarray datasets as a common reference, so that statistical attributes of each probeset, such as dynamic range or a threshold between low and high expression can be reliably discovered through meta-analysis. This strategy is implemented in web-based platform named Gene Expression Commons (http://gexc.stanford.edu/ ) with datasets of 39 distinct highly purified mouse hematopoietic stem/progenitor/functional cell populations covering almost the entire hematopoietic system. Since the Gene Expression Commons is designed as an open platform, any scientist can explore gene expression of any gene, search by expression pattern of interest, submit their own microarray datasets, and design their own working models.
Publication Title
Gene Expression Commons: an open platform for absolute gene expression profiling.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 8 Downloadable Samples
Description
Using EphB2 or the ISC marker Lgr5, we have FACS-purified and profiled intestinal stem cells (ISCs), crypt proliferative progenitors and late transient amplifying cells to define a gene expression program specific for normal ISCs.
Publication Title
The intestinal stem cell signature identifies colorectal cancer stem cells and predicts disease relapse.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 26 Downloadable Samples
Description
Epigenetic modifications must underlie lineage-specific differentiation since terminally differentiated cells express tissue-specific genes, but their DNA sequence is unchanged. Hematopoiesis provides a well-defined model of progressive differentiation in which to study the role of epigenetic modifications in cell fate decisions. Multi-potent progenitors (MPPs) can differentiate into all blood cell lineages, while downstream progenitors commit to either myeloerythroid or lymphoid lineages. While DNA methylation is critical for myeloid versus lymphoid differentiation, as demonstrated by the myeloerythroid bias in Dnmt1 hypomorphs {Broske, 2009 #6}, a comprehensive DNA methylation map of hematopoietic progenitors, or of any cell lineage, does not exist. Here we have generated a mouse DNA methylation map, examining 4.6 million CpG sites throughout the genome including all CpG islands and shores, examining MPPs, all lymphoid progenitors (ALPs), common myeloid progenitors (CMPs), granulocyte/macrophage progenitors (GMPs), and thymocyte progenitors (DN1, DN2, DN3). Interestingly, differentiation towards the myeloid lineage corresponds with a net decrease in DNA methylation, while lymphoid commitment involves a net increase in DNA methylation, but both show substantial dynamic changes consistent with epigenetic plasticity during development. By comparing lineage-specific DNA methylation to gene expression array data, we find many examples of genes and pathways not previously known to be involved in lymphoid/myeloid differentiation, such as Gcnt2, Arl4c, Gadd45, and Jdp2. Several transcription factors, including Meis1 and Prdm16 were methylated and silenced during differentiation, suggesting a role in maintaining an undifferentiated state. Additionally, epigenetic modification of modifiers of the epigenome appears to be important in hematopoietic differentiation. Our results directly demonstrate that modulation of DNA methylation occurs during lineage-specific differentiation, often correlating with gene expression changes, and define a comprehensive map of the methylation and transcriptional changes that accompany myeloid versus lymphoid fate decisions.
Publication Title
Comprehensive methylome map of lineage commitment from haematopoietic progenitors.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 6 Downloadable Samples
Description
XEN cells are derived from the primitive endoderm of mouse blastocysts. In culture and in chimeras they exhibit properties of parietal endoderm. However, BMP signaling promotes XEN cells to form an epithelium and differentiate into visceral endoderm (VE). Of the several different subtypes of VE described, BMP induces a subtype that is most similar to the VE adjacent to the trophoblast-derived extraembryonic ectoderm.
Publication Title
BMP signaling induces visceral endoderm differentiation of XEN cells and parietal endoderm.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 1 Downloadable Sample
Description
We compare the transcriptome of two different clones of multipotent adult progenitor cells (MAPCs) using Affymetrix arrays.
Publication Title
Hematopoietic reconstitution by multipotent adult progenitor cells: precursors to long-term hematopoietic stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 14 Downloadable Samples
Description
To characterized the changes in gene expression during the differentiation of TS cells. TS cells can be derived from two time point during embryogenesis, cell lines tested were from each of these time points.
Publication Title
Gata3 regulates trophoblast development downstream of Tead4 and in parallel to Cdx2.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
Description
To identify whether Cdx2 or Gata3 can activate trophoblast specific gene expression when expressed in R1 ES cells. To assess the dependency of Gata3 activity on Cdx2, Gata3 was also expressed in Cdx2-null ES cells.
Publication Title
Gata3 regulates trophoblast development downstream of Tead4 and in parallel to Cdx2.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 4 Downloadable Samples
Description
An important question for the use of the mouse as a model for studying human disease is the degree of functional conservation of genetic control pathways from human to mouse. The human placenta and mouse placenta show structural similarities but there has been no systematic attempt to assess their molecular similarities or differences. We built a comprehensive database of protein and microarray data for the highly vascular exchange region micro-dissected from the human and mouse placenta near-term. Abnormalities in this region are associated with two of the most common and serious complications of human pregnancy, maternal preeclampsia (PE) and fetal intrauterine growth restriction (IUGR), each disorder affecting ~5% of all pregnancies.
Publication Title
Comparative systems biology of human and mouse as a tool to guide the modeling of human placental pathology.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
The perinatal period and early infancy are considered critical periods for lung development, and adversities during this period are believed to impact lung health in adulthood.The main factors affecting postnatal lung development and growth include environmental exposures, cigarette smoking, (viral) infections, allergic sensitization, and asthma.Therefore, we hypothesized that concomitant exposure in the early postnatal period in mice would cause more profound alterations in lung alveolarization and growth in adult life, quantified by stereology, and differently modulate lung inflammation and gene expression than either insult alone.Five-day-old male mice were immunized intraperitoneally (i.p.) with 10 µg of ovalbumin (OVA). This procedure was repeated at the 7th day of life, animals from the control group received i.p. injection of PBS only. Mice were exposed to either ambient PM2.5 or filtered air from the 5th to the 39th day of life, using an ambient particle concentrator developed at the Harvard School of Public Health (HAPC).Total RNA of lung samples (n=3 animals per group) was extracted using RNeasy Mini Kit (Qiagen, Hilden, Germany), according to manufacturer's instructions. The microarray analysis was performed using three RNA samples for each studied group (Control, OVA, PM2.5, OVA+PM2.5), totalizing 12 samples. One hundred nanograms of total RNA was amplified with the Ambion WT Expression Kit and hybridized onto the GeneChip Mouse Gene 2.0 ST Array (Thermo Scientific, Massachusetts, USA), following manufacturer’s protocol. The comparison between the control and OVA group exhibit 32 DEGs (28 up-regulated and 4 down-regulated), between the control and PM2.5 group had 6 DEGs (4 up and 2 down) and between the control and OVA+PM2.5 group had 5 DEGs (4 up and 1 down). The comparison between OVA and PM2.5 group showed 97 DEGS (22 up and 75 down) and between OVA and OVA+PM2.5 group had 7 DEGs (4 up and 3 down). Finally, the comparison between the PM2.5 and OVA+PM2.5 group exhibit 34 DEGs (2 up and 32 down).Our experimental data provide pathological support for the hypothesis that either allergic or environmental insults in early life have permanent adverse consequences to lung growth. In addition, combined insults were associated with the development of a COPD-like phenotype in young adult mice.
Publication Title
Allergic sensitization and exposure to ambient air pollution beginning early in life lead to a COPD-like phenotype in young adult mice.
Sample Metadata Fields
Treatment
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