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GSE35844
Mus musculus
9 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
MiRNAs have the potential to regulate cellular differentiation programs. However, miRNA-deficiency in primary hematopoietic stem cells (HSCs) results in HSC depletion in mice, leaving the question of whether miRNAs play a role in early-lineage decisions unanswered. To address this issue, we deleted Dicer1, which encodes an essential RNaseIII enzyme for miRNA biogenesis, in murine CCAAT/enhancer-binding protein alpha (C/EBPA)-positive myeloid-committed progenitors in vivo. In contrast to the results in HSCs, we found that miRNA depletion affected neither the number of myeloid progenitors nor the percentage of C/EBPA-positive progenitor cells. Analysis of gene-expression profiles from wild type and Dicer1-deficient granulocyte-macrophage progenitors (GMPs) revealed that 20 miRNA families were active in GMPs. Of the derepressed miRNA targets in Dicer1-null GMPs, 27% are normally exclusively expressed in HSCs or are specific for multi-potent progenitors and erythropoiesis, indicating an altered gene-expression landscape. Dicer1-deficient GMPs were defective in myeloid development in vitro and exhibited an increased replating capacity, indicating a regained self-renewal potential of these cells. In mice, Dicer1 deletion blocked monocytic differentiation, depleted macrophages and caused myeloid dysplasia with morphological features of Pelger-Hut anomaly. These results provide evidence for a miRNA-controlled switch for a cellular program of self-renewal and expansion towards myeloid differentiation in GMPs.
Publication Title
Dicer1 deletion in myeloid-committed progenitors causes neutrophil dysplasia and blocks macrophage/dendritic cell development in mice.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To identify cellular and genetic abnormalities involved in interstrand cross link repair-deficient bone marrow failure and its transformation to leukemia, we used an Ercc1 hypomorphic mouse model (Ercc1 -/d).
Publication Title
ICL-induced miR139-3p and miR199a-3p have opposite roles in hematopoietic cell expansion and leukemic transformation.
Sample Metadata Fields
Age, Specimen part
View Samples- Danio rerio
- 160 Downloadable Samples
NextSeq 500
Description
We present ScarTrace, a single-cell sequencing strategy that allows us to simultaneously quantify information on clonal history and cell type for thousands of single cells obtained from different organs from adult zebrafish. Using this approach we show that all blood cells types in the kidney marrow arise from a small set of multipotent embryonic. In contrast, we find that cells in the eyes, brain, and caudal tail fin arise from many embryonic progenitors, which are more restricted and produce specific cell types in the adult tissue. Next we use ScarTrace to explore when embryonic cells commit to forming either left or right organs using the eyes and brain as a model system. Lastly we monitor regeneration of the caudal tail fin and identify a subpopulation of resident macrophages that have a clonal origin that is distinct from other blood cell types. Overall design: Single cell sequencing data from cells isolated from zebrafish organs (whole kidney marrow, forebrain, hindbrain, left eye, right eye, left midbrain, right midbrain, and regenerated fin). For each cell, we provide libraries with transcritpome and with clonal information, respectively.
Publication Title
Whole-organism clone tracing using single-cell sequencing.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Rod and cone photoreceptors in mammalian retina are generated from common pool(s) of neuroepithelial progenitors. NRL, CRX and NR2E3 are key transcriptional regulators that control photoreceptor differentiation. Mutations in NR2E3, a rod-specific orphan nuclear receptor, lead to loss of rods, increased density of S-cones, and supernormal S-cone-mediated vision in humans. To better understand its in vivo function, NR2E3 was expressed ectopically in the Nrl-/- retina, where post-mitotic precursors fated to be rods develop into functional S-cones similar to the human NR2E3 disease. Expression of NR2E3 in the Nrl-/- retina completely suppressed cone differentiation and resulted in morphologically rod-like photoreceptors, which were not functional. Gene profiling of FACS-purified photoreceptors confirmed the role of NR2E3 as a strong suppressor of cone genes and an activator of a subset of rod genes (including rhodopsin) in vivo. Ectopic expression of NR2E3 in cone precursors and differentiating S-cones of wild type retina also generates rod-like cells. The dual regulatory function of NR2E3 is not dependent upon the presence of NRL and/or CRX, but on the timing and level of its expression. Our studies reveal a critical role of NR2E3 in establishing functional specificity of post-mitotic photoreceptor precursors during retinal neurogenesis.
Publication Title
In vivo function of the orphan nuclear receptor NR2E3 in establishing photoreceptor identity during mammalian retinal development.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
It is known that CBFB-MYH11, the fusion gene generated by inversion of chromosome 16 in human acute myeloid leukemia, is causative for oncogenic transformation. However, the mechanism by which CBFB-MYH11 initiates leukemogenesis is not clear. Previously published reports showed that CBFB-MYH11 dominantly inhibits RUNX1 and CBFB, and such inhibition has been suggested as the mechanism for leukemogenesis. However, knockin mice expressing Cbfb-MYH11 (Cbfb+/MYH11) showed defects in primitive hematopoiesis not seen in Cbfb null (Cbfb-/-) embryos indicating that Cbfb-MYH11 has repression independent activities as well.
Publication Title
Cbfb/Runx1 repression-independent blockage of differentiation and accumulation of Csf2rb-expressing cells by Cbfb-MYH11.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The C-terminus of CBF-SMMHC, the fusion protein produced by a chromosome 16 inversion in acute myeloid leukemia subtype M4Eo, contains domains for self-mulimerization and transcriptional repression, both of which have been proposed to be important for leukemogenesis by CBF-SMMHC. To test the role of the fusion protein's C-terminus in vivo, we generated knock-in mice expressing a C-terminally truncated CBF-SMMHC (CBF-SMMHCC95). Embryos with a single copy of CBF-SMMHCDC95 were viable and showed no defects in hematopoiesis, while embryos homozygous for the CBF-SMMHCC95 allele had hematopoietic defects and died in mid-gestation, similar to embryos with a single-copy of the full-length CBF-SMMHCC95.
Publication Title
The C-terminus of CBFβ-SMMHC is required to induce embryonic hematopoietic defects and leukemogenesis.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 14 Downloadable Samples
- IlluminaHiSeq4000
Description
In zebrafish, parental exposure to ionizing radiation has been associated with effects in offspring, such as increased DNA damage and reactive oxygen species. Here, we assessed short (one month) and long term effects (one year) on gene expression in embryonic offspring (5.5 hours post fertilization) from zebrafish exposed during gametogenesis to gamma radiation (8.7 or 53 mGy/h for 27 days, total dose 5.2 or 31 Gy). One month after exposure, a global change in gene expression was observed in offspring from the 53 mGy/h group, followed by embryonic death at late gastrula, whereas offspring from the 8.7 mGy/h group was unaffected. One year after exposure, embryos from the 8.7 mGy/h group exhibited 2455(61.8% downregulated) differentially expressed genes. Overlaps in differentially expressed genes and enriched biological pathways were evident between the 53 mGy/h group one month and 8.7 mGy/h one year after exposure, which could be linked to effects in adults and offspring, such as DNA damage and lipid peroxidation. Interestingly, pathways between the two groups were oppositely regulated. Our results indicate latent effects following ionizing radiation exposure in parents that can be transmitted to offspring and warrants monitoring effects over subsequent generations. Overall design: One month after exposure, mRNA from F1 5.5 hpf embryos from parents exposed to 8.7 and 53 mGy/h gamma radiation during gametogenesis was sequenced on the Illumina 4000 platform with three replicas per treatment. One year after exposure, mRNA from F1 embryos from the same parents exposed to 8.7 mGy/h was sequenced with three biological replicates. In both cases, F1 embryos from non-exposed parents were used as control and mRNA sequenced in triplicates, taken at the same time points as the exposed samples.
Publication Title
Parental exposure to gamma radiation causes progressively altered transcriptomes linked to adverse effects in zebrafish offspring.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 11 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Progression from low- to high-grade in a glioblastoma model reveals the pivotal role of immunoediting.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The different phases of tumor immunoediting in vivo were dissected thanks to a murine model of glioma induced by PDGF-B overexpression. We show that low-grade gliomas are highly immunostimulatory and that the adaptive immune system prevents the development of secondary tumor in syngeneic mice. During tumor progression, glioma cells downregulate immunostimulatory genes and the immune infiltrate becomes pro-tumorigenic. We showed that glioma cells are able to progress towards a high-grade phenotype even in immunodeficient mice, albeit more slowly and this progression invariably requires a downregulation of immunostimulatory genes.
Publication Title
Progression from low- to high-grade in a glioblastoma model reveals the pivotal role of immunoediting.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Results showed that Chd7 deficiency delay Cbfb-MYH11 induced leukemia, to explore the mechanism, We also performed microarray analysis on c-Kit+ leukemic cells to determine gene expression differences between Mx1-Cre, Cbfb+/56M and Chd7f/f, Mx1-Cre, Cbfb+/56M leukemic cells.
Publication Title
<i>Chd7</i> deficiency delays leukemogenesis in mice induced by <i>Cbfb-MYH11</i>.
Sample Metadata Fields
Specimen part
View Samples