Continuous sperm production is not necessary for the survival of the organism, but is essential to maintain a species. The process of spermatogenesis is comprised of three phases: mitotic proliferation, meiosis, and spermiogenesis. To illuminate germline intrinsic and extrinsic programs, we performed single-cell RNA sequencing on ~35K cells from the adult mouse testis. This analysis provides a comprehensive molecular atlas of the testis, identifying both known and novel cell types. We demonstrate for the first time the continuous nature of germ cell differentiation, provide molecular signatures and subtype-specific molecular markers, and identify several novel candidate regulators of spermatogenesis. Finally, we demonstrate in vivo using spatial mapping that germ and somatic cell molecular subtypes correspond to previously defined histological cell types residing at different stages of seminiferous epithelial cycle. Taken together, our results unveil the complexity of the testis, and provide a global, unbiased roadmap of the in vivo gametogenesis program. Overall design: Drop-seq of whole mouse testis and enriched populations. NOTE: As the initial submission of raw data only included partial run (extracted mouse cells) for some samples, all raw data for the following samples have been replaced to include the complete/original run for each sample (Feb 2019): GSM3069439, GSM3069440, GSM3069443-GSM3069448,GSM3069450, GSM3069451, GSM3069459-GSM3069463 All raw data for the 25 samples are paired-end, with 8 single-species samples + 17 mixed-species samples. For mixed-species samples, the major species is mouse, and the spike-in can be either human or monkey. The spike-in species were only used to confirm cells are not doublets by two-species mixing experiments, but not analyzed in processed data under GSE112393.
A Comprehensive Roadmap of Murine Spermatogenesis Defined by Single-Cell RNA-Seq.
Age, Specimen part, Cell line, Subject
View SamplesThis dataset contains whole-genome RNA sequencing results from rat embryonic hippocampal neuronal cultures and serves as the basis for characterization of CRISPR/dCas9 gene activation in neuronal systems. Overall design: This experiment contains 9 biological samples, each of which underwent directional, paired-end PolyA+ RNA-seq on an Illumina Next-seq 500. Samples were treated with Lacz sgRNA (LZ2, LZ4, & LZ5), Bdnf-I sgRNA (B16, B17, B18), or Bdnf-IV sgRNA (BIV11, BIV14, BIV15), in addition to a dCas9-VPR fusion. Datasets were obtained using RNA-seq from PolyA+ fractions fractions of RNA. Each sample has multiple files, corresponding to different sequencing lanes (e.g., L001, L002, etc) or different reads (e.g., R1, R2).
A Neuron-Optimized CRISPR/dCas9 Activation System for Robust and Specific Gene Regulation.
Specimen part, Cell line, Treatment, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The BTB and CNC homology 1 (BACH1) target genes are involved in the oxidative stress response and in control of the cell cycle.
Cell line, Time
View SamplesBTB and CNC homology 1 (BACH1) is a heme-binding transcription factor repressing the transcription from a subset of MAF recognition elements (MAREs) at low intracellular heme levels. Upon heme binding, BACH1 is released from the MAREs, resulting in increased expression of antioxidant response genes. To systematically address the gene regulatory networks involving BACH1, we performed knock-down of BACH1 in HEK 293T cells using three independent types of small interfering RNAs followed by transcriptome profiling using microarrays.
The BTB and CNC homology 1 (BACH1) target genes are involved in the oxidative stress response and in control of the cell cycle.
Cell line, Time
View SamplesA central challenge in pharmaceutical research is to investigate genetic variation in response to drugs. The Collaborative Cross (CC) mouse reference population is a promising model for pharmacogenomic studies because of its large amount of genetic variation, genetic reproducibility, and dense recombination sites. While the CC lines are phenotypically diverse, their genetic diversity in drug disposition processes, such as detoxification reactions, is still largely uncharacterized. Here we systematically measured RNA-sequencing expression profiles from livers of 29 CC lines under baseline conditions. We then leveraged a reference collection of metabolic biotransformation pathways to map potential relations between drugs and their underlying expression quantitative trait loci (eQTLs). By applying this approach on proximal eQTLs, including eQTLs acting on the overall expression of genes and on the expression of particular transcript isoforms, we were able to construct the organization of hepatic eQTL-drug connectivity across the CC population. The analysis revealed a substantial impact of genetic variation acting on drug biotransformation, allowed mapping of potential joint genetic effects in the context of individual drugs, and demonstrated crosstalk between drug metabolism and lipid metabolism. Our findings provide a resource for investigating drug disposition in the CC strains, and offer a new paradigm for integrating biotransformation reactions to corresponding variations in DNA sequences. Overall design: This dataset includes RNA-Seq data of mRNA that were extracted from the liver of 55 male mice. The 55 mice belong to 29 different collaborative cross strains. The number of individual mice per strains is 3 for 3 strains, 2 for 16 strains, and 1 for 8 strains. All the mice are naïve without any special treatment.
Dissecting the Effect of Genetic Variation on the Hepatic Expression of Drug Disposition Genes across the Collaborative Cross Mouse Strains.
Specimen part, Cell line, Subject
View SamplesTranscriptome of HEK and B cells were analyzed by microarray and RNA-Seq parallely. Both platforms were then compared in terms of sensitivity. To assess whether values were a reliable indicator of gene activity, we correlated these values with hypophosphorylated RNA polymerase II (PolIIa) occupancy, used as a landmark of transcription initiation. For HEK, we identified PolIIa islands by chromatin immunoprecipitation and sequencing (ChIP-Seq).
A global view of gene activity and alternative splicing by deep sequencing of the human transcriptome.
No sample metadata fields
View SamplesInduced pluripotent stem cells hold great promise for modeling human hematopoietic diseases. However, intrinsic variability in the capacities of different iPSC lines for hematopoietic development complicates comparative studies and is currently unexplained.
Clonal genetic and hematopoietic heterogeneity among human-induced pluripotent stem cell lines.
Specimen part, Cell line
View SamplesMaternal Blood histamine levels are tightly controlled in normal pregnancy. However, in specific complications of human pregnancy such as pre-eclampsia the levels of both placental and maternal blood histamine increase. Increasing blood histamine levels nonetheless, have been associated with oxidative stress, endothelial dysfunction, abnormal tissue growth, and Th1/TH2 imbalance, which are also linked to pre-eclampsia. Little is known of the molecular responses in the placenta to the prolonged exposure to increasing histamine levels in the presence of changing oxygen concentrations.
Oxygen and tissue culture affect placental gene expression.
Specimen part, Treatment
View SamplesAnalysis of the gene expression pattern in the caput, corpus and cauda epididymides of three donors of 26-50 years of age with no medical pathologies that could affect reproductive function. The data generated in this study demonstrate a region specific gene expression pattern along the human epididymis that seems to coincide with the morphological distinctive features of the excurrent duct.
Region-specific gene expression profiling along the human epididymis.
No sample metadata fields
View SamplesWe previously demonstrated that Alox5deficiency impairs the function of LSCs and prevents the initiation of BCR-ABL-induced CML. To identify the pathways in whichAlox5gene regulates function of LSCs, we performed a comparative DNA microarray analysis using total RNA isolated from non-BCR-ABL-expressing Lin-Sca-1+c-Kit+, BCR-ABL-expressing wild type LSCs and BCR-ABL-expressing Alox5-/- LSCs. The result was validated by quantitative real-time PCR analysis of non-BCR-ABL-expressing Lin-Sca-1+c-Kit+, BCR-ABL-expressing wild type LSCs and BCR-ABL-expressing Alox5-/- LSCs.
A tumor suppressor function of the Msr1 gene in leukemia stem cells of chronic myeloid leukemia.
Age, Specimen part
View Samples