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SRP146068
Mus musculus
14 Downloadable Samples
Illumina HiSeq 2000
Description
Bone marrow stromal cells (BMSCs) were isolated from the femora and tibiae of irtTA-GBD*-TAg transgenic mice. Using cellular cloning we established skeletal progenitors with distinct differentiation properties and analysed their transcriptome. Unipotent osteogenic and adipogenic cells expressed specific transcriptional programs whereas bipotent clones combined expression of those genes and did not show a unique signature. Overall design: Expression profiling (RNA-seq) of two independent clones from different mice representing skeletal progenitors with the following characteristics: tripotent clones (Osteogenic, Adipogenic, Chondrogenic = OAC1 and OAC2); bipotent clones (Osteogenic, Adipogenic = OA1 and OA2); unipotent clones (Osteogenic = O1 and O2; Adipogenic = A1 and A2). Further, we prepared and sequenced pools of several other clones from these two mice, with the following properties: tripotent clones (Osteogenic, Adipogenic, Chondrogenic = OAC3); bipotent clones (Osteogenic, Adipogenic = OA3; Osteogenic, Chondrogenic = OC3; Adipogenic, Chondrogenic = AC3); unipotent clones (Osteogenic = O3; Adipogenic = A3).
Publication Title
Clonal Analysis Delineates Transcriptional Programs of Osteogenic and Adipogenic Lineages of Adult Mouse Skeletal Progenitors.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina HiSeq 2000
Description
Transcriptome analysis of somatic stem cells and their progeny is fundamental to identify new factors controlling proliferation versus differentiation during tissue formation. Here we generated a combinatorial, fluorescent reporter mouse line to isolate proliferating neural stem cells, differentiating progenitors and newborn neurons that coexist as intermingled cell populations during brain development. Transcriptome sequencing revealed numerous novel long non-coding (lnc)RNAs and uncharacterized protein-coding transcripts identifying the signature of neurogenic commitment. Importantly, most lncRNAs overlapped neurogenic genes and shared with them a nearly identical expression pattern suggesting that lncRNAs control corticogenesis by tuning the expression of nearby cell fate determinants. We assessed the power of our approach by manipulating lncRNAs and protein-coding transcripts with no function in corticogenesis reported to date. This led to several evident phenotypes in neurogenic commitment and neuronal survival indicating that our study provides a remarkably high number of uncharacterized transcripts with hitherto unsuspected roles in brain development. Finally, we focussed on one lncRNA, Miat, whose manipulation was found to trigger pleiotropic effects on brain development and aberrant splicing of Wnt7b. Hence, our study suggests that lncRNA-mediated alternative splicing of cell fate determinants controls stem cell commitment during neurogenesis. “LncRNAs control neurogenesis” Aprea, Prenninger, Dori, Monasor, Wessendof, Zocher, Massalini, Ghosh, Alexopoulou, Lesche, Dahl, Groszer, Hiller, Calegari, The EMBO Journal (In Press) Overall design: mRNA profiles of Proliferating Progenitors, Differentiating Progenitors and Neurons from lateral cortex of E14.5 mouse embryos. Each cell type in three biological replicates.
Publication Title
Transcriptome sequencing during mouse brain development identifies long non-coding RNAs functionally involved in neurogenic commitment.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 30 Downloadable Samples
- Illumina HiSeq 2500
Description
The identification of small molecules which either increase the number and/or enhance the activity of CD34+ hematopoietic stem and progenitor cells (HSPCs) during ex-vivo expansion has remained challenging. Applying an unbiased in vivo chemical screen in a transgenic (c-myb:EGFP) zebrafish embryo model, histone deacetylase inhibitors (HDACI) (valproic acid, resminostat and entinostat) were shown to significantly amplify the number of phenotypic hematopoietic precursors. The identified HDACIs were confirmed to significantly enhance also the expansion of human HSPCs during ex vivo treatment. Long-term functionality of ex vivo expanded human HSPCs was verified in a xenotransplantation model using NSG mice. However, the HDACI induced proliferation of HSPCs was associated with short-term functional changes. One of the identified hits, valproic acid (VPA), increased the adhesion capacity of CD34+ cells on primary mesenchymal stromal cells and reduced their chemokine-mediated migration capacity in vitro. In line with the reduced migratory potential in vitro, homing as well as early engraftment of VPA treated human CD34+ cells was significantly impaired in the xenotransplantation model. Our data confirms that HDACI treatment leads to a net expansion of HSPCs cells with long-term engraftment potential across different species. However impaired homing and short-term-engraftment has to be kept in mind when designing clinical transplantation protocols. In addition, our gene expression analysis (RNA-Seq) revealed expression of several genes that were altered in CD34+ cells by VPA treatment including cell adhesion molecules and Notch and wnt genes which has been shown to be involved in preservation of stem cell properties. Overall design: Gene expression analysis of in vitro expanded human HSPCs (CD34+ cells) by valproic acid
Publication Title
Zebrafish In-Vivo Screening for Compounds Amplifying Hematopoietic Stem and Progenitor Cells: - Preclinical Validation in Human CD34+ Stem and Progenitor Cells.
Sample Metadata Fields
Disease, Subject
View Samples- Mus musculus
- 60 Downloadable Samples
- Illumina HiSeq 2000
Description
To elucidate responses of myeloid cells to SAMHD1 deficiency in the absence of exogenous viral infection, we performed global gene expression analysis of SAMHD1 deficient macrophages. Overall design: Peritoneal macrophages from 10 mutants and 10 controls were FACS sorted. Isolated RNA was subjected to next generation mRNA sequencing.
Publication Title
Mouse SAMHD1 has antiretroviral activity and suppresses a spontaneous cell-intrinsic antiviral response.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line
View Samples- Mus musculus
- 22 Downloadable Samples
- Illumina HiSeq 2000
Description
To investigate the contribution of type-1 IFN signalling to the upregulation of IFN- stimulated genes in SAMHD1-deficient cells, we performed global gene expression analysis of SAMHD1-deficient IFNAR-/- macrophages. Overall design: Peritoneal macrophages from ten SAMHD1-deficient IFNAR-/- and six SAMHD1-deficient controls were FACS sorted. RNA was subjected to next generation mRNA sequencing.
Publication Title
Mouse SAMHD1 has antiretroviral activity and suppresses a spontaneous cell-intrinsic antiviral response.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
To elucidate responses of myeloid cells to SAMHD1 deficiency in the absence of exogenous viral infection, we performed global gene expression analysis of SAMHD1 deficient macrophages. Overall design: Peritoneal macrophages from nine mutants and nine controls were FACS sorted. Cells from three animals were pooled to yield three poolls per group. RNA from these pools was subjected to next generation mRNA sequencing
Publication Title
Mouse SAMHD1 has antiretroviral activity and suppresses a spontaneous cell-intrinsic antiviral response.
Sample Metadata Fields
Sex, Age, Cell line, Subject
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina HiSeq 2500
Description
Transplantation of GABAergic interneurons (INs) can sustain long-standing benefits in animal models of epilepsy and other neurological disorders. In a therapeutic perspective, a renewable source of functional GABAergic INs is needed. Here, we identified five factors (Foxg1, Sox2, Ascl1, Dlx5 and Lhx6) able to convert fibroblasts directly into induced GABAergic INs (iGABA-INs), displaying the molecular signature of telencephalic INs. The selected factors recapitulate in fibroblasts the activation of transcriptional networks required for the specification of GABAergic fate during telencephalon development. iGABA-INs exhibited progressively maturing firing patterns comparable to those of cortical INs, had synaptic currents and released GABA. Importantly, upon grafting in the hippocampus, iGABA-INs survived, matured and their optogenetic stimulation triggered GABAergic transmission and inhibited the activity of connected granule cells. The five factors also converted human cells into functional GABAergic neurons. These properties define iGABA-INs as a promising tool for disease modeling and cell-based therapeutic approaches. Overall design: Comparison of iGABA-INs transcriptional profile with those of starting fibroblasts and GAD67-GFP+ cortical interneurons.
Publication Title
Rapid Conversion of Fibroblasts into Functional Forebrain GABAergic Interneurons by Direct Genetic Reprogramming.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 15 Downloadable Samples
- IlluminaHiSeq2500
Description
Constitutive low level DNA damage in RNASEH2 deficiency is linked to innate immune activation. Hierarchical clustering of over 16000 transcripts revealed remarkably similar profiles in patients with lupus erythematosus and patients with AGS with up-regulation of genes involved in DNA damage signaling and type I-IFN signaling. Overall design: Comparison of transcriptional profiles of native RNASEH2-deficient patient fibroblasts with wild type cells.
Publication Title
Defective removal of ribonucleotides from DNA promotes systemic autoimmunity.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 17 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Specificity and heterogeneity of terahertz radiation effect on gene expression in mouse mesenchymal stem cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We report that terahertz (THz) irradiation of mouse mesenchymal stem cells with a pulsed broadband (centered at 10 THz) source, or a single-frequency, 2.52 THz, (SF) laser source, both with weak average power (<1mW/cm2), results in specific heterogenic changes in gene expression. The insignificant differential expression of heat shock and stress related genes as well as our temperature measurements imply a non-thermal response. The microarray survey and RT-PCR experiments demonstrate that at different irradiation conditions distinct groups of genes are activated. Stem cells irradiated for 12 hours with the broadband THz source exhibit an accelerated differentiation toward adipose phenotype, while the 2-hour (broadband or SF) irradiation affects genes transcriptionally active in pluripotent stem cells. Phenotypic and gene expression differences suggest that the THz effect depends on irradiation parameters such as duration and type of THz source, and on the level of stem cell differentiation. Computer simulations of the core promoters of two pluripotency markers reveal association between gene upregulation and propensity for DNA breathing. We propose that THz radiation has potential for non-contact control of cellular gene expression.
Publication Title
Specificity and heterogeneity of terahertz radiation effect on gene expression in mouse mesenchymal stem cells.
Sample Metadata Fields
Specimen part
View Samples