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Agilent microarray analysis between a Dullard-heterozygous and a Dullard-homozygous E7.5 embryo

ABSTRACT: To explore the loss of Dullurd function in mouse embryo development, we have performed the Agilent microarray analysis between a Dullard-heterozygous and a Dullard-homozygous E7.5 embryo. Our findings show that Dullard does not act in concert with BMP4 and Smad1/5/8, whereas loss of Dullard is associated with a reduced level of WNT/Î²-catenin signaling activity, accompanied by elevated expression of Wnt3 and WNT antagonists including Dkk1, Sfrp1 and Sfrp5 in mouse germ cell formation. E7.5 mouse embryos were collected. One Dullard-heterozygous embryo and one Dullard-homozygous embryo were used for the analysis.

ORGANISM(S): Mus musculus

SUBMITTER: Satomi Tanaka

PROVIDER: E-GEOD-39224 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Agilent microarray analysis between a Dullard-heterozygous and a Dullard-homozygous E7.5 embryo

Project description:To explore the loss of Dullurd function in mouse embryo development, we have performed the Agilent microarray analysis between a Dullard-heterozygous and a Dullard-homozygous E7.5 embryo. Our findings show that Dullard does not act in concert with BMP4 and Smad1/5/8, whereas loss of Dullard is associated with a reduced level of WNT/β-catenin signaling activity, accompanied by elevated expression of Wnt3 and WNT antagonists including Dkk1, Sfrp1 and Sfrp5 in mouse germ cell formation.

2013-03-31 | GSE39224 | GEO

Mus musculus

Project description:Agilent microarray analysis between a Dullard-heterozygous and a Dullard-homozygous E7.5 embryo

| PRJNA170249 | ENA

Gene expression signatures for fractions of E7.5 whole embryos based on Endoglin and Flk-1 markers

Project description:Much remains unknown about the signals that induce early mesoderm to initiate hematopoietic differentiation. Here we show that endoglin (Eng), a receptor for the TGFÎ² superfamily, identifies all cells with hematopoietic fate in the early embryo. These arise in an Eng+Flk1+ mesodermal precursor population at E7.5, a cell fraction also endowed with endothelial potential. In Eng knockout embryos, hematopoietic colony activity and numbers of CD71+Ter119+ erythroid progenitors were severely reduced. This coincided with severely reduced expression of embryonic globin and key BMP target genes including the hematopoietic regulators Scl, Gata1, Gata2 and Msx-1. To interrogate molecular pathways active in the earliest hematopoietic progenitors, we applied transcriptional profiling to sorted cells from E7.5 embryos. Eng+Flk-1+ progenitors co-expressed TGFÎ² and BMP receptors and target genes. Furthermore, Eng+Flk-1+ cells presented high levels of phospho-SMAD1/5, indicating active TGFÎ² and/or BMP signaling. Remarkably, under hematopoietic serum-free culture conditions, hematopoietic outgrowth of endoglin-expressing cells was dependent on TGFÎ² superfamily ligands: BMP4, BMP2, or TGF-Î²1. These data demonstrate that the E+F+ fraction at E7.5 represents mesodermal cells competent to respond to TGFb1, BMP4, or BMP2, shaping their hematopoietic development, and that endoglin is a critical regulator in this process by modulating TGF/BMP signaling. E7.5 pooled embryos (25 litters; 300 embryos approximately) were dissected and 3,000 cells were sorted in triplicate for Eng-Flk1-, Eng-Flk1+, Eng+Flk1+, and Eng+Flk1- fractions. Microarray results were analyzed with GeneSpring GX software.

2012-04-22 | E-GEOD-37515 | biostudies-arrayexpress

Transcription profiling by high throughput sequencing of primordial germ cells from e6.5, e7.5, e8.5 embryos and e7.5 somatic neighbours and Blimp1-KO mice

Project description:Primordial germ cell mRNA profiles from cells microdissected from e6.5, e7.5 and e8.5 embryos, e7.5 somatic neighbours and Blimp1-KO mice were generated by single cell library construction and sequencing in duplicate using Applied Biosystems SOLiD sequencer. Single cell library construction is described in: Tang f. et. al, Nature Protocols (2010), Vol. 5, p.516.

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Genes affected by SFRP5 overexpression in LSK cells and CLP

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Gene expression signatures for fractions of E7.5 whole embryos based on Endoglin and Flk-1 markers

Project description:Much remains unknown about the signals that induce early mesoderm to initiate hematopoietic differentiation. Here we show that endoglin (Eng), a receptor for the TGFβ superfamily, identifies all cells with hematopoietic fate in the early embryo. These arise in an Eng+Flk1+ mesodermal precursor population at E7.5, a cell fraction also endowed with endothelial potential. In Eng knockout embryos, hematopoietic colony activity and numbers of CD71+Ter119+ erythroid progenitors were severely reduced. This coincided with severely reduced expression of embryonic globin and key BMP target genes including the hematopoietic regulators Scl, Gata1, Gata2 and Msx-1. To interrogate molecular pathways active in the earliest hematopoietic progenitors, we applied transcriptional profiling to sorted cells from E7.5 embryos. Eng+Flk-1+ progenitors co-expressed TGFβ and BMP receptors and target genes. Furthermore, Eng+Flk-1+ cells presented high levels of phospho-SMAD1/5, indicating active TGFβ and/or BMP signaling. Remarkably, under hematopoietic serum-free culture conditions, hematopoietic outgrowth of endoglin-expressing cells was dependent on TGFβ superfamily ligands: BMP4, BMP2, or TGF-β1. These data demonstrate that the E+F+ fraction at E7.5 represents mesodermal cells competent to respond to TGFb1, BMP4, or BMP2, shaping their hematopoietic development, and that endoglin is a critical regulator in this process by modulating TGF/BMP signaling.

2012-04-23 | GSE37515 | GEO

A genotype directed dose-finding study of Irinotecan (CPT-11) by groups of Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) polymorphisms in patients with advanced metastatic colorectal cancer and gastric cancer.

Project description:Interventions: Administraion of CPT-11 is twice for 4 weeks on days 1 and 15. CPT-11 is reconstituted in >=250 mL of normal saline or 5% dextrose in water and infuse 90min on day 1 for pharmacokinetics, and 90min over on day15. CPT-11 adjusted dosage is determined from 50,75,100,125 or 150mg/sqm in the heterozygous group and the homozygous group by continual reassessment method. CPT-11 dosage is fixed at 150mg/sqm in the wild group.Definision of UGT1A1 polymorphisms groups: The homozygous group is patient with homozygous genotype of UGT1A1*28/*28 or UGT1A1*6/*6, with combined heterozygous genotypes of UGT1A1*28 and UGT1A1*6. The heterozygous group is patient with heterozygous genotype of either UGT1A1*28 or UGT1A1*6. The wild group is patients with no UGT1A1*28 and UGT1A1*6 mutation. Primary outcome(s): Maximum tolerated dose for the heterozygous group and the homozygous group, respectively. Incidence rate of dose limiting toxicities for the wild group. Study Design: Single arm Non-randomized

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Personalized use of irinotecan in colorectal cancer patients based on real world studies and pharmacogenomics

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