Brain structure and function experience dramatic changes from embryonic to postnatal development. However, gene expression information during early brain development is limited. We have generated >27 million reads to identify mRNAs from the mouse cortex for >16,000 genes at either embryonic day 18 (E18) or postnatal day 7 (P7), a period of significant synaptogenesis for neural circuit formation. In addition, we devised strategies to detect alternative splice forms and previously unannotated transcriptionally active regions (TARs).
Transcriptome of embryonic and neonatal mouse cortex by high-throughput RNA sequencing.
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A unique H2A histone variant occupies the transcriptional start site of active genes.
Sex, Age, Specimen part
View SamplesChromatin performs numerous functions during cellular differentiation, and therefore it must be capable of adopting a multitude of different structures. How these various structures are established is poorly understood, but we propose that specific histone H2A variants will have a key role in remodelling chromatin during differentiation. Structurally, we show here that the gain of just a single acidic amino acid residue has generated a new mouse H2A.Bbd-like histone variant, H2A.Lap1, and that when incorporated into nucleosomal arrays imparts on them unique biophysical properties that are distinct from arrays containing either H2A or human H2A.Bbd. Functionally, we identify H2A.Lap1 as a novel chromatin component of active genes that are expressed during spermatogenesis, and in combination with H2A.Z create a unique chromatin landscape at the start site of transcription. During round spermatid differentiation, H2A.Lap1 dramatically loads onto the inactive X chromosome enabling a subset of its genes to be transcriptionally activated.
A unique H2A histone variant occupies the transcriptional start site of active genes.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Histone H2A.Z inheritance during the cell cycle and its impact on promoter organization and dynamics.
Specimen part, Cell line
View SamplesWhile it has been clearly established that well positioned H2A.Z-containing nucleosomes flank the nucleosome depleted region (NDR) at the transcriptional start site (TSS) of active mammalian genes 1,2, how this chromatin-based information is transmitted through the cell cycle is unknown. We show here that in trophoblast stem (TS) cells, the level of H2A.Z at promoters decreases during S phase coinciding with homotypic (H2A.Z/H2A.Z) nucleosomes flanking the TSS becoming heterotypic (H2A.Z/H2A). Surprisingly, these nucleosomes remain heterotypic at M phase. At the TSS, we identify an unstable heterotypic H2A.Z-containing nucleosome in G1 which, strikingly, is lost following DNA replication. These dynamic changes in H2A.Z at the TSS mirror a global expansion of the NDR at S and M which, unexpectedly, is unrelated to transcriptional activity. Coincident with the loss of H2A.Z at promoters, it is targeted to the centromere when mitosis begins.
Histone H2A.Z inheritance during the cell cycle and its impact on promoter organization and dynamics.
Specimen part, Cell line
View SamplesHow genomic information is selectively utilized to direct spatial and temporal gene expression patterns during differentiation remains to be elucidated but it is clear that regulated changes in higher-order genomic architecture plays a fundamental role. Specifically, long range interactions within and between chromosomes and the position of chromosome territories in the nucleus are controlled by TADs and LADs respectively, but the relationship between these genomic organizers remains poorly understood Overall design: We analyzed the large-scale spatial reorganization of chromatin by generating matched Hi-C and nuclear lamin-chromatin contact datasets throughout a dual adipose/neuronal induction of human primary adipose stem cells. We have mapped Hi-C (TADs) and lamin-associated domains (LADs) in multiple steps during adipose stem cell differentiation to characterize the spatial and temporal link between genomic architecture and gene expression. We identify a new level of 4D genomic organization involving a long-range clustering of individual TADs or TAD pairs into TAD cliques. LADs appear to regulate their formation. (ASCs). We unveil a lineage-specific dynamic assembly and disassembly of repressive cliques of linearly non-contiguous TADs, and a time course-coupled relationship between TAD clique size and lamina association. Our findings reveal a new level of developmental genome organization and provide an overview of large-scale changes in the 4D nucleome during lineage-specific differentiation.
Long-range interactions between topologically associating domains shape the four-dimensional genome during differentiation.
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View SamplesHuntingtons disease (HD) is an incurable hereditary neurodegenerative disorder, which manifests itself as a loss of GABAergic medium spiny (GABA MS) neurons in the striatum and caused by an expansion of the CAG repeat in exon 1 of the huntingtin gene. There is no cure for HD, existing pharmaceutical can only relieve its symptoms. Here, induced pluripotent stem cells were established from patients with low CAG repeat expansion in the huntingtin gene, and were then efficiently differentiated into GABA MS-like neurons under defined culture conditions. Analysis of differentially expressed genes between Huntingtons disease and wild type iPSCs derived GABA MS-like neurons has been performed.
Manifestation of Huntington's disease pathology in human induced pluripotent stem cell-derived neurons.
Age, Specimen part
View SamplesRNA sequencing analysis of gene expression in serrated colon polyps, uninvolved colon and control colon Overall design: 86 colon RNA sequencing datasets (21 sessile serrated adenomas/polyps, 10 hyperplastic polyps, 10 adenomatous polyps, 21 uninvolved colon, 20 control colon and 4 colon cancer)
Gene Signature in Sessile Serrated Polyps Identifies Colon Cancer Subtype.
No sample metadata fields
View SamplesRNA-sequencing of SSP RNA from patients with serrated polyposis syndrome identifies VSIG1 and MUC17 as potential diagnostic markers for SSPs Overall design: 5'' capped RNA from seven ascending SSPs, six patient matched uninvolved right colon and two normal right colon samples was used for RNA sequencing (15 samples total)
RNA sequencing of sessile serrated colon polyps identifies differentially expressed genes and immunohistochemical markers.
Sex, Disease, Subject
View SamplesHypoxia may cause pulmonary and brain edema, pulmonary hypertension, aberrant metabolism and early mortality. To better understand pathological processes associated with hypoxia, we examined gene expression in Chuvash polycythemia (CP) blood mononuclear cells. CP is a congenital disorder of up-regulated hypoxic response at normoxia wherein VHLR200W homozygosity leads to elevated hypoxia inducible factor (HIF)-1 and HIF-2 levels, thromboses, pulmonary hypertension, lower systemic blood pressure (SBP) and increased mortality. VHLR200W homozygotes are often treated by phlebotomy resulting in iron deficiency, allowing us to evaluate an interaction of augmented hypoxia sensing with iron deficiency.
Iron deficiency modifies gene expression variation induced by augmented hypoxia sensing.
Sex, Specimen part
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