One of the central issues in evolutionary developmental biology is how we can formulate the relationships between evolutionary and developmental processes. Two major models have been proposed: the 'funnel-like' model, in which the earliest embryo shows the most conserved morphological pattern, followed by diversifying later stages, and the 'hourglass' model, in which constraints are imposed to conserve organogenesis stages, which is called the phylotypic period. Here we perform a quantitative comparative transcriptome analysis of several model vertebrate embryos and show that the pharyngula stage is most conserved, whereas earlier and later stages are rather divergent. These results allow us to predict approximate developmental timetables between different species, and indicate that pharyngula embryos have the most conserved gene expression profiles, which may be the source of the basic body plan of vertebrates.
Comparative transcriptome analysis reveals vertebrate phylotypic period during organogenesis.
Sex, Specimen part, Disease, Disease stage
View SamplesTranscription profiling of X.laevis development.
Comparative transcriptome analysis reveals vertebrate phylotypic period during organogenesis.
Sex, Specimen part
View SamplesTranscription profiling of chicken development
Comparative transcriptome analysis reveals vertebrate phylotypic period during organogenesis.
Sex, Specimen part
View SamplesTranscription profiling of mouse development
Comparative transcriptome analysis reveals vertebrate phylotypic period during organogenesis.
Sex, Specimen part, Disease, Disease stage
View SamplesTo identify genes regulated by AP3/PI, we carried out microarray experiments using an Arabidopsis whole genome GeneChip array (ATH1 GeneChip, Affymetrix, Santa Clara, CA) in conjunction with an inducible AP3-GR system. For these experiments, we used 35S::AP3-GR transgenic plants in a 35S::PI, ap3-3 null mutant background for various dex or mock treatments. RNA was extracted from inflorescences at 0 and 4 hours after dex or a mock treatment and used as probes for our microarray experiments. Three biological replicates of each were hybridized to Affymetrix ATH1 arrays. We used the Affymetrix Microarray Suite software (MAS) to identify genes whose expression profiles changed only after dex-treatment and are likely targets of AP3/PI.
Two GATA transcription factors are downstream effectors of floral homeotic gene action in Arabidopsis.
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View SamplesIn order to identify putative downstream target genes of RBE, we sequenced mRNA from dexamethasone (DEX) and mock treated transgenic Arabidopsis line 35S:GR-RBE (RBE coding region fused to a glucocorticoid receptor domain driven by the constitutive 35S promoter) floral tissues. We compared the results from DEX and mock treatments and focused on the 832 genes whose expression was significantly reduced (P < 0.025) by 2-fold or more in DEX as compared to mock-treated plants. In this analysis, we identified MIR164c (EEP1) as a candidate target of RBE, which was further confirmed by other molecular and genetic analyses. Regulation of MIR164c by RBE is important for normal floral organ formation in Arabidopsis. Overall design: We used two biological replicates, each with two technical replicates for four hour DEX or mock treated floral tissues to produce 8 sequencing libraries.
RBE controls microRNA164 expression to effect floral organogenesis.
Specimen part, Cell line, Subject
View SamplesHuman induced pluripotent stem (iPS) cells derived from somatic cells of patients hold great promise for modelling human diseases. Dermal fibroblasts are frequently used for reprogramming, but require an invasive skin biopsy and a prolonged period of expansion in cell culture prior to use. Here, we report the derivation of iPS cells from multiple human blood sources including peripheral blood mononuclear cells (PBMCs) harvested by routine venipuncture. Peripheral blood-derived human iPS lines are comparable to human embryonic stem (ES) cells with respect to morphology, expression of surface antigens, activation of endogenous pluripotency genes, DNA methylation and differentiation potential. Analysis of Immunoglobulin and T-cell receptor gene rearrangement revealed that some of the PBMC iPS cells were derived from T-cells, documenting derivation of iPS cells from terminally differentiated cell types. Importantly, peripheral blood cells can be isolated with minimal risk to the donor and can be obtained in sufficient numbers to enable reprogramming without the need for prolonged expansion in culture. Reprogramming from blood cells thus represents a fast, safe and efficient way of generating patient-specific iPS cells.
Reprogramming of T cells from human peripheral blood.
Specimen part, Cell line
View SamplesRett syndrome (RTT) is a devastating neurodevelopmental disorder that occurs once in every 10,000-15,000 live female births. Despite intensive research, no effective cure is yet available. Valproic acid (VPA) has been used widely to treat mood disorder, epilepsy, and a growing number of other disorders. In limited clinical studies, VPA has also been used to control seizure in RTT patients with promising albeit somewhat unclear efficacy. In this study we tested the effect of VPA on the neurological symptoms of RTT and discovered that short-term VPA treatment during the symptomatic period could reduce neurological symptoms in RTT mice. We found that VPA restores the expression of a subset of genes in RTT mouse brains, and these genes clustered in neurological disease and developmental disorder networks. Our data suggest that VPA could be used as a drug to alleviate RTT symptoms.
VPA alleviates neurological deficits and restores gene expression in a mouse model of Rett syndrome.
Specimen part
View SamplesEtiolated Arabidopsis seedlings open their cotyledons and halt rapid elongation of hypocotyl when exposed to light (de-etiolation). Major light responsive components in this process have been identified and signaling pathways revealed, yet how the organ-specific light responses are achieved remains unknown. Here we report that a developmental regulator TCP4 (TEOSINTE BRANCHED1, CYCLOIDEA, and PCF) participates in photomorphogenesis and facilitates light-induced cotyledon-opening. We demonstrate that TCP4-like transcriptional factors, which predominantly express in cotyledons of both light and dark seedlings, activate SAUR16 and SAUR50 in response to light. Light repressor PIF3 (or PIFs, phytochrome-interacting factors), which accumulates in etiolated seedlings and rapidly declines upon light exposure, inhibits TCP4 promoter-binding and prevents activation of SAUR16/50 in darkness. Our study reveals how an interplay between light responsive factors and developmental regulators leads to signal-dependent and tissue-specific regulation of gene expressions, which ultimately resulted in organ-specific light responses during de-etiolation. Overall design: Cotyledon mRNA profiles of 4-day-old dark grown Col, mTCP4#4 and mTCP4#10 seedlings were generated by deep sequencing.
The Transcription Factors TCP4 and PIF3 Antagonistically Regulate Organ-Specific Light Induction of <i>SAUR</i> Genes to Modulate Cotyledon Opening during De-Etiolation in Arabidopsis.
Specimen part, Subject
View SamplesIn humans, germline competency and the specification of primordial germ cells (PGCs) are thought to occur in a restricted developmental window during early embryogenesis. Despite the importance of specifying the appropriate number of PGCs for human reproduction, the molecular mechanisms governing PGC formation remain largely unexplored. Here, we compared PGC-like cell (PGCLC) differentiation from 18 independently derived human embryonic stem cell (hESC) lines, and discovered that the expression of primitive streak genes were positively associated with hESC germline competency. Furthermore, we show that chemical inhibition of TGFß and WNT signaling, which are required for primitive streak formation and CRISPR/Cas9 deletion of Eomesodermin (EOMES), significantly impacts PGCLC differentiation from hESCs. Taken together, our results suggest that human PGC formation involves signaling and transcriptional programs associated with somatic germ layer induction and expression of EOMES. Overall design: There are 91 RNAseq samples in total.
Germline competency of human embryonic stem cells depends on eomesodermin.
Specimen part, Subject
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