The role of microRNAs (miRNA) in first cell fate choice of the preimplantation mouse embryo remains unresolved, as gene expression and knockout data are conflicting. This cell fate choice generates the extraembryonic lineage of the trophoblast and the embryonic lineage of the epiblast (inner cell mass). The trophoblast differentiates into polar and mural cells, where polar cells contribute to placental development and mural cells to the implantation process and Reicherts membrane. The inner cell mass further differentiates into the epiblast and primitive endoderm. We used stem cell lines that can be derived from the trophoblast and epiblast lineages to address the role of miRNAs in early lineage cell fate specification and determination. Using embryonic stem cells (ESC) and trophoblast stem cells (TSC) as starting and ending states of cell development we identified a network of TSC expressed miRNAs that are enriched in ESC targets mRNA. We used constitutive and inducible expression of TSC enriched miRNAs in ESC and show that they can drive cell morphology and gene expression profiles similar to trophoblast. Additionally we show that this process required HDAC2 inhibition and is miRNA specific, as cardiac specific miR-1 could not induce trophoblast under these conditions. In contrast to embryo derived and Cdx2 induced trophoblast cells, miRNAs promote a mural TE like cell phenotype. Transplantation into preimplantation mouse embryos showed that miRNA-induced trophoblast preferentially contributes to the mural trophoblast in both the blastocyst and the Reicherts membrane. Our data support a role for miRNAs and HDACs in the specification of the trophoblast and potentially the polar and mural cell types.
Overexpression of Trophoblast Stem Cell-Enriched MicroRNAs Promotes Trophoblast Fate in Embryonic Stem Cells.
No sample metadata fields
View SamplesWe report the whole transcriptome data of single-cells derived from the early 16-cell stage to the 64-cell stage in the mouse embryo. Overall design: RNA from 262 cells from 36 mouse embryos (16- to 64-cell stage)
Position- and Hippo signaling-dependent plasticity during lineage segregation in the early mouse embryo.
Cell line, Subject
View SamplesInduced pluripotent stem (iPS) cell reprogramming is a gradual epigenetic process that reactivates the pluripotent transcriptional network by erasing and establishing heterochromatin marks. Here, we characterize the physical structure of heterochromatin domains in full and partial mouse iPS cells by correlative Electron Spectroscopic Imaging (ESI). In somatic and partial iPS cells, constitutive heterochromatin marked by H3K9me3 is highly compartmentalized into chromocenter structures of densely packed 10 nm chromatin fibers. In contrast, chromocenter boundaries are poorly defined in pluripotent ES and full iPS cells, and are characterized by unusually dispersed 10 nm heterochromatin fibers in high Nanog-expressing cells, including pluripotent cells of the mouse blastocyst prior to differentiation. This heterochromatin reorganization accompanies retroviral silencing during conversion of partial iPS cells by Mek/Gsk3 2i inhibitor treatment. Thus, constitutive heterochromatin reorganization serves as a novel biomarker with retroviral silencing for identifying iPS cells in the very late stages of reprogramming.
Constitutive heterochromatin reorganization during somatic cell reprogramming.
Specimen part, Cell line
View SamplesExpression profiling of stem cell lines derived from the early embryo representing the trophoblast, primitive endoderm, early epiblast (inner cell mass E3.5) and late post-implantation epiblast (E5.5).
Cell-surface proteomics identifies lineage-specific markers of embryo-derived stem cells.
Sex, Specimen part, Cell line
View SamplesWe sequenced the mRNAs of embryonic stem cells (ESCs) cultured in different conditions. The two lines M (male) and F (female) used in this study were derived from E4 blastocysts of the same cross between a C57BL/6J (Mus musculus domesticus) and CAST/EiJ (Mus castaneus) male. mESCs were cultured in 2i and LIF as the ground state condition or in serum and LIF as the conventional condition. Epistem cell lines were also generated from the two lines by culturing them with Activin A and FGF2. In order to study more advanced development, we differentiated the two mESC lines through embryonic body formation to postmitotic motor neurons using retinoic acid and the smoothened agonist SAG. This differentiation process also results in the derivation of several types of interneurons. We picked single cells from all different conditions and generated sequencing libraries using the Smart-seq2 and Tn5 protocol. For simplicity, we designate the different condition as ES2i, ES, Epi and Neuron from hereon. We also obtained preimplantation inner cell mass and epiblast cells from E3.5 ICM (inner cell mass) and E4.5 blastocysts of the crossbred mice (male CAST/EiJ × female C57BL/6J) as well as postimplantation epiblast cells from E5.5 embryos of C57BL/6J mice Overall design: Examination of gene expression profile in individual male and female embryonic stem cell lines along developmental progression
Single-cell analyses of X Chromosome inactivation dynamics and pluripotency during differentiation.
Sex, Specimen part, Cell line, Subject
View SamplesToxin A and B from Clostridium difficile are the primary virulence factors in Clostridium difficile disease. The changes in gene transcription of human colon epithelial cells were investigated in vitro in order to better understand the many effects of both toxins.
Systems analysis of the transcriptional response of human ileocecal epithelial cells to Clostridium difficile toxins and effects on cell cycle control.
Cell line
View SamplesWe report a mouse model that recapitulates expression of the ETV6-NTRK3 (EN) fusion oncoprotein, the product of the t(12;15)(p13;q25) translocation characteristic of human secretory breast carcinoma. Activation of EN expression in mammary tissues by Whey acidic protein (Wap) promoter-driven Cre leads to fully penetrant, multifocal malignant breast cancer with short latency. We provide genetic evidence that committed bipotent or CD61+ luminal alveolar progenitors, are targets of tumorigenesis. Furthermore, EN transforms these otherwise transient progenitors through activation of the AP1 complex. Given increasing relevance of chromosomal translocations in epithelial cancers, such mice serve as a paradigm for the study of their genetic pathogenesis and cellular origins, and generation of novel preclinical models.
ETV6-NTRK3 fusion oncogene initiates breast cancer from committed mammary progenitors via activation of AP1 complex.
No sample metadata fields
View SamplesWe report a mouse model that recapitulates expression of the ETV6-NTRK3 (EN) fusion oncoprotein, the product of the t(12;15)(p13;q25) translocation characteristic of human secretory breast carcinoma. Activation of EN expression in mammary tissues by Whey acidic protein (Wap) promoter-driven Cre leads to fully penetrant, multifocal malignant breast cancer with short latency. We provide genetic evidence that committed bipotent or CD61+ luminal alveolar progenitors, are targets of tumorigenesis. Furthermore, EN transforms these otherwise transient progenitors through activation of the AP1 complex.
ETV6-NTRK3 fusion oncogene initiates breast cancer from committed mammary progenitors via activation of AP1 complex.
No sample metadata fields
View SamplesWe report a mouse model that recapitulates expression of the ETV6-NTRK3 (EN) fusion oncoprotein, the product of the t(12;15)(p13;q25) translocation characteristic of human secretory breast carcinoma. Activation of EN expression in mammary tissues by Whey acidic protein (Wap) promoter-driven Cre leads to fully penetrant, multifocal malignant breast cancer with short latency. We provide genetic evidence that committed bipotent or CD61+ luminal alveolar progenitors, are targets of tumorigenesis. Furthermore, EN transforms these otherwise transient progenitors through activation of the AP1 complex. Given increasing relevance of chromosomal translocations in epithelial cancers, such mice serve as a paradigm for the study of their genetic pathogenesis and cellular origins, and generation of novel preclinical models.
ETV6-NTRK3 fusion oncogene initiates breast cancer from committed mammary progenitors via activation of AP1 complex.
No sample metadata fields
View SamplesRecent advances in high density oligonucleotides microarray technology have brought solutions for molecular profiling of human samples at an unprecedented resolution. We mapped whole blood RNA from healthy volunteers and CD34+ from cytapheresis to Human Exon ST 1.0 microarrays. We compared mature blood cells samples with immature CD34+ samples and each of these compartiement with a broad panel of solid tissues. By scanning the expression of over one million known or predicted exons, transcripts such as INPP4B, NEDD9 CD74 and VAV3 were identified as alternatively transcribed between haematopoietic system and solid tissues. The very large combinatorial complexity conveyed by alternative splicing contributes to the specific functional properties of blood cells and haematopoietic stem cells. The gene expression profiles are freely accessible through a dynamic web atlas, providing to the medical and scientific community a simple mean to interrogate and visualize this reference dataset. Finally, the relevance and the precision provided by this exon expression map suggest that exon arrays may be a powerful tool to link specific peripheral whole blood exon signatures modifications to many diseases such as cancer or auto-immune disorders.
Expression map of the human exome in CD34+ cells and blood cells: increased alternative splicing in cell motility and immune response genes.
Specimen part
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