Here we provide fundamental insights into early human development by single-cell RNA-sequencing of human and mouse preimplantation embryos. We elucidate conserved transcriptional programs along with those that are human-specific. Importantly, we validate our RNA-sequencing findings at the protein level, which further reveals differences in human and mouse embryo gene expression. For example, we identify several genes exclusively expressed in the human pluripotent epiblast including the transcription factor KLF17. Key components of the TGF-ß signaling pathway including NODAL, GDF3, TGFBR1/ALK5, LEFTY1, SMAD2, SMAD4 and TDGF1 are also enriched in the human epiblast. Intriguingly, inhibition of TGF-ß signaling abrogates NANOG expression in human epiblast cells, consistent with a requirement for this pathway in pluripotency. Although key trophectoderm factors Id2, Elf5, and Eomes are exclusively localized to this lineage in the mouse, the human orthologues are either absent or expressed in alternative lineages. Importantly, we also identify genes with conserved expression dynamics including Foxa2/FOXA2, which we show is restricted to the primitive endoderm in both human and mouse embryos. Comparisons of the human epiblast to existing embryonic stem cells (hESCs) reveals conservation of pluripotency but also additional pathways more enriched in hESCs. Our analysis highlights significant differences in human preimplantation development compared to mouse and provides a molecular blueprint to understand human embryogenesis and its relationship to stem cells. Overall design: Single-Cell RNA-seq
Defining the three cell lineages of the human blastocyst by single-cell RNA-seq.
No sample metadata fields
View SamplesMicroarray analysis of parity induced gene expression changes in the mammary glands of four strains of rats to identify a common gene signature associated with protection against methylnitrosourea induced mammary tumorigenesis.
Hormone-induced protection against mammary tumorigenesis is conserved in multiple rat strains and identifies a core gene expression signature induced by pregnancy.
Age, Specimen part
View SamplesAnalysis of transcription response of undifferentiated human BE(2)-C neuronal cells to stimulation with purified antimycin A1a or unfractionated commercially available antimycin A (Sigma A8674).
Discovery of potent broad spectrum antivirals derived from marine actinobacteria.
Specimen part
View SamplesAnalysis of transcription response of undifferentiated human BE(2)-C neuronal cells to stimulation with novel indole-2-carboxamide antivirals 205432 or 206381.
Novel indole-2-carboxamide compounds are potent broad-spectrum antivirals active against western equine encephalitis virus in vivo.
Specimen part, Treatment
View SamplesMitochondrial DNA (mtDNA) mutations are maternally inherited and are associated with a broad range of debilitating and fatal diseases. Assisted reproductive technologies designed to uncouple the inheritance of mtDNA from nuclear DNA may enable women who carry mtDNA mutations to have a genetically related child with a greatly reduced risk of disease. Here we report for the first time that pronuclear transplantation (PNT) between normally fertilised human zygotes provides an effective approach to preventing transmission of mtDNA disease. We found that the procedures previously used to perform PNT between abnormally fertilized human zygotes are highly inefficient when applied to those that undergo normal fertilization. We have therefore developed an alternative approach based on transplanting PN shortly after completion of the second meiotic division rather than shortly before onset of the first mitosis. This approach promotes highly efficient development to the blastocyst stage without affecting nuclear genome integrity. Furthermore, the expression profile of genes encoded by the nuclear and mitochondrial genomes was indistinguishable from unmanipulated control embryos. Importantly, levels of mtDNA transferred with the nuclear genome are below the threshold for mtDNA disease. Together these data indicate that transplantation of pronuclei early in the first cell cycle holds promise as a safe and effective approach to preventing transmission of mtDNA disease. Overall design: Single-Cell RNA-seq analysis of embryos generated by pronuclear transfer and unmanipulated control embryos The relationship between single cell samples and the embryo from which they were derived is indicated in the sample ''characteristics: sample type'' field.
Towards clinical application of pronuclear transfer to prevent mitochondrial DNA disease.
No sample metadata fields
View SamplesThrough development of an in vivo orthotopic lung cancer model, we reveal an unanticipated pathway driving spontaneous metastasis that is orchestrated by the developmentally-regulated transcriptional repressor, Capicua (CIC). Overall design: RNAseq and DNA copy number analysis of H1975 (EGFR-mutant lung adenocarcinoma) cells in the context of drug resistance to rociletinib
Inactivation of Capicua drives cancer metastasis.
No sample metadata fields
View SamplesGene expression profile of primary human CD34+/CD38lo cells differentiating along the megakaryocyte lineage.
Gene expression profile of primary human CD34+CD38lo cells differentiating along the megakaryocyte lineage.
Specimen part, Time
View SamplesPurpose: To analyze the mRNA content of Foxd1Cre;Smo(flox/-) mutant kidneys. Methods: We collected E13.5 wildtype and Foxd1Cre;Smo(flox/-) mutant kidneys and isolated RNA to do RNA-Seq. Results: Identified differentially expressed transcripts in Foxd1Cre;Smo(flox/-) mutant kidneys compared to wildtype controls. Conclusions: Our work provides novel insight into how Hedgehog signaling from stromal cells influences renal development. Overall design: RNA sequencing of Foxd1Cre;Smo(flox/-) mutant kidneys compared to controls.
Hedgehog-GLI signaling in <i>Foxd1-</i>positive stromal cells promotes murine nephrogenesis via TGFβ signaling.
Specimen part, Subject
View SamplesTo determine gene expression changes during in vitro senescence of MSC we have analyzed differential expression of the corresponding early passage (P2) and senescent passage (PX). There were global changes in the gene expression profile that were reproducible in three independent donor samples.
Replicative senescence of mesenchymal stem cells: a continuous and organized process.
No sample metadata fields
View SamplesmRNA profiles of astrocytes infected with Borrelia burdorferi for 24 hours, 48 hours, and 24 hour uninfected controls were generated by deep sequencing, in triplicate, using Illumina HiSeq. Overall design: mRNA profiles of astrocytes infected with Borrelia burdorferi for 24 hours, 48 hours, and 24 hour uninfected controls were generated by deep sequencing, in triplicate, using Illumina HiSeq.
MicroRNA and mRNA Transcriptome Profiling in Primary Human Astrocytes Infected with Borrelia burgdorferi.
Specimen part, Subject, Time
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