We 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 SamplesExpression profiling of progenitor cells from human supraclavicular and subcutaneous adipose tissue. Studies in animal models revealed that brown and white adipocytes derive from different progenitor cells. Molecular characteristics of these cells have not been investigated in detail in humans.
Comparative gene array analysis of progenitor cells from human paired deep neck and subcutaneous adipose tissue.
Sex, Age
View SamplesSensorineural hearing loss affects the majority of the elderly population. Mammalian hair cells (HC) do not regenerate and current stem cell and gene delivery protocols result only in immature hair cells like-cells. For this reason, characterization of the transcriptional cascades that lead to development and survival of inner ear HC is essential for designing molecular-based treatments for deafness. We employed a cell type-specific approach to analyze the transcriptomes of the mouse early postnatal auditory and vestibular sensory epithelia and of hair cells derived from zebrafish model. Overall design: Murine auditory and vestibular epithelia were separated into hair-cells (HCs) and epithelial non-sensory cells (ENSCs) by flow cytometry. Gene expression levels were recorded in independent triplicates from the sorted cells using RNA-seq
RFX transcription factors are essential for hearing in mice.
No sample metadata fields
View SamplesSensorineural hearing loss affects the majority of the elderly population. Mammalian hair cells (HC) do not regenerate and current stem cell and gene delivery protocols result only in immature hair cells like-cells. For this reason, characterization of the transcriptional cascades that lead to development and survival of inner ear HC is essential for designing molecular-based treatments for deafness. We employed a cell type-specific approach to analyze the transcriptomes of the mouse early postnatal auditory and vestibular sensory epithelia and of hair cells derived from zebrafish model. Overall design: We utilized the ppv3b:GFP transgenic zebrafish, which express GFP predominantly in HC. We sorted GFP-positive and negative cells from 5 day post fertilization (dpf) larvae using flow cytometry, and profiled their transcriptomes using RNA-seq
RFX transcription factors are essential for hearing in mice.
No sample metadata fields
View SamplesType 1 diabetes is characterized by the destruction of pancreatic beta cells, and generating new insulin-producing cells from other cell types is a major aim of regenerative medicine. One promising approach is transdifferentiation of developmentally related pancreatic cell types including glucagon-producing alpha cells. In a genetic model, overexpression of the master regulatory transcription factor Pax4 or loss of its counterplayer Arx are sufficient to induce the conversion of alpha cells to functional beta-like cells. Here we identify artemisinins as small molecules that functionally repress Arx and induce beta-cell characteristics in alpha cells. We show that the protein gephyrin is the mammalian target of these antimalaria drugs. Finally, we demonstrate that gephyrin-mediated enhancement of GABAA receptor signaling is the mechanism of action of these molecules in pancreatic transdifferentiation. Our results indicate that gephyrin is a novel druggable target for the regeneration of pancreatic beta cell mass from alpha cells. Overall design: Transcriptional dissection of Artemether treated, human pancreatic islets of one donor using single-cell RNA-seq
Artemisinins Target GABA<sub>A</sub> Receptor Signaling and Impair α Cell Identity.
Subject
View SamplesType 1 diabetes is characterized by the destruction of pancrea tic beta cells, and generating new insulin-producing cells from other cell types is a major aim of regenerative medicine. One promising approach is transdifferentiation of developmentally related pancreatic cell types including glucagon-producing alpha cells. In a genetic model, loss of the master regulatory transcription factor Arx is sufficient to induce the conversion of alpha cells to functional beta-like cells. Here we identify artemisinins as small molecules that functionally repress Arx by causing its translocation to the cytoplasm. We show that the protein gephyrin is the mammalian target of these antimalaria drugs, and that enhancement of GABAA receptor signaling contributes to the mechanism of action of these molecules in pancreatic transdifferentiation. Our results in zebrafish, rodents and primary human pancreatic islets indicate that gephyrin is a novel druggable target for the regeneration of pancreatic beta cell mass from alpha cells. Overall design: There are two parts in the transcriptional study on mouse cell lines in this project. One part is on Min6-ARX inducible cells with different induction time of Dox. This is done in three different clones. The other part is on alpha-TC1 cells. This is done in one concentration of Artemether, one time point and two biological repeats.
Artemisinins Target GABA<sub>A</sub> Receptor Signaling and Impair α Cell Identity.
Specimen part, Cell line, Subject
View SamplesWe used mammosphere formation assay and label-retention assay as functional cellular approaches to enrich for cells with different degree of cancer stem cell properties in the breast cancer cell line MDA-MB-231 and performed single-cell RNA sequencing Overall design: Single cells from three different populations: 30 cells from G1 cell cycle phase cultured in adherent conditions, 46 cells with low proliferation cultured in non-adherent conditions (mammosphere assasy), 45 cells with high proliferation cultured in non-adherent conditions (mammosphere assay)
Erratum: Identification of Breast Cancer Stem Cell Related Genes Using Functional Cellular Assays Combined With Single-Cell RNA Sequencing in MDA-MB-231 Cells.
Cell line, Subject
View SamplesThe importance of the role of microRNAs in gene expression and disease is well recognized. However, what is less appreciated is that almost half of miRNA genes are organized in polycistronic clusters and are therefore co-expressed. The mir-11~998 cluster consists of two miRNAs, miR-11 and miR-998. Here, we describe a novel layer of regulation that links the processing and expression of miR-998 to the presence of the mir-11 gene. We show that the presence of mir-11 in the pri-miRNA is required for processing by Drosha, and deletion of mir-11 prevents the expression of miR-998. Replacing mir-11 with an unrelated miRNA rescued miR-998 expression in vivo and in vitro, as did expressing miR-998 from a shorter, more canonical miRNA scaffold. The embedded regulation of miR-998 is functionally important because unchecked miR-998 expression in the absence of miR-11 resulted in highly penetrant pleiotropic developmental defects. We further show that this novel regulation of expression of miRNAs within a cluster is not limited to the mir-11~998 cluster and likely reflects the more general cis-regulation of expression of individual miRNAs. Thus, our results reveal a novel layer of regulation within miRNA clusters that tempers the functions of the individual miRNAs. Unlinking their expression has the potential to change the expression of multiple miRNA targets and shift biological response. Overall design: RNA was extracted from Drosophila third instar larval eye discs of animals grown in standard conditions; Illumina HiSeq2000 Next Gen RNA Sequencing was performed, and differential expression of genes was assessed in wild-type vs unchecked miR-998 expression
Novel regulation and functional interaction of polycistronic miRNAs.
Specimen part, Subject
View SamplesExpression of dE2F1 induces proliferation and apoptosis. We sought to perform an unbiased analysis of the effect of co-expression of miR-11
mir-11 limits the proapoptotic function of its host gene, dE2f1.
Specimen part
View SamplesThird instar larval eye discs provide an in vivo model for cell cycle exit studies. Posterior to the Second Mitotic Wave proliferation is absent in a wild type eye disc. Inactivating mutations in tumor suppressor-like genes can lead to genome wide changes in gene expression that allow for inappropriate bypass of cell cycle exit signals posterior to the Second Mitotic Wave.
Cooperation between dE2F1 and Yki/Sd defines a distinct transcriptional program necessary to bypass cell cycle exit.
Specimen part
View Samples