Transcriptome analysis of Casz1 was performed using litters of postnatal day 2 retinas from crosses between Casz1Flox/Flox; R26-Stop-EYFP and Casz1Flox/Flox; IKCre-A; R26-Stop-EYFP. The IK-A Cre driver is described in Tarchini et al., Dev Dyn 241(12):1973-85. EYFP marks Cre expressing (and therefore cKO) cells. Cells were incubated for 30 min in RGM serum-free medium described in Cayouette et al., Neuron 40(5):897, supplemented with Hoechst 33342 (Invitrogen), and 4N cells were sorted using a MOFLO cytometer (Beckman) based on Hoechst, GFP expression, and propidium iodide exclusion. Overall design: Cells were sorted directly into lysis buffer on ice and RNA was immediately extracted using RNeasy mini columns (Qiagen). Two independent experiments were performed, and the RNA samples were processed in parallel. RNA amplification was performed using Truseq PE Cluster kit v3 PE50 (Illumina). Deep sequencing was performed using Truseq stranded mRNA (Illumina) with mRNA enrichment and strand-specific parameters, using a Hiseq 2000 instrument (Illumina).
Casz1 controls higher-order nuclear organization in rod photoreceptors.
Specimen part, Cell line, Subject
View SamplesMost differentiation protocols for generation of hepatocyte-like cells from iPS cells generate cells with heterogenous expression of hepatic markers, which confounds results from liver disease models involving complex traits and subtle phenotypes
Mapping the Cell-Surface N-Glycoproteome of Human Hepatocytes Reveals Markers for Selecting a Homogeneous Population of iPSC-Derived Hepatocytes.
Specimen part
View SamplesEffect of the ablation of connexin 30 in the stria vascularis
Connexin30 deficiency causes instrastrial fluid-blood barrier disruption within the cochlear stria vascularis.
Age, Specimen part, Disease, Time
View SamplesWe performed RNA sequencing on melanopsin deleted retinas (Opn4-DTA/DTA) to determine potential cues involved in instructing cone photoreceptor positioning Overall design: RNAseq of whole P8 retinal extracts from wild-type littermate vs. Opn4DTA/DTA mice
Melanopsin Retinal Ganglion Cells Regulate Cone Photoreceptor Lamination in the Mouse Retina.
Specimen part, Subject
View SamplesBackground. More than one million women in fertile age are infected with Trypanosoma cruzi worldwide. Anti-T.cruzi seropositivity in mothers has been associated with adverse pregnancy outcome but there is still a knowledge gap regarding this effect. Our aim was to compare the gene expression profile of term placental environment from T. cruzi seropositive (SP) and seronegative (SN) mothers. Methods. A RNA-Seq was performed in 9 pools of 2 different placental RNA samples each: 3 belonging to placentas from SN and 6 from SP. Each pool consisted of a binomial of a female/male newborn and a vaginal/caesarean delivery. None of the newborns resulted infected. Results. Only 42 genes showed a significant fold change between SP and SN groups. Among the down-regulated genes were KISS1 and CGB5. In the up-regulated genes group were: KIF12, HLA-G, PRG2, TAC3, FN1 and ATXN3L. To identify pathways significantly associated with maternal T. cruzi-infection, a gene-set association analysis was implemented. The placental environment transcriptomic profile of SP consisted of an enrichment in immunological genes sets (inflammatory response and lymphocytic activation were over-expressed) whereas numerous biosynthetic processes were down-regulated. Conclusions. It is worth noting that several differentially expressed genes in SP placentas code for proteins associated to preeclampsia and miscarriage. This first transcriptomics study in human term placental environment from non-infected deliveries shows a placental response that may affect the faetus while protecting it from the parasite infection; this host response could be responsible for the low rate of congenital transmission observed in human chronic Chagas disease. Background. More than one million women in fertile age are infected with Trypanosoma cruzi worldwide. Anti-T.cruzi seropositivity in mothers has been associated with adverse pregnancy outcome but there is still a knowledge gap regarding this effect. Our aim was to compare the gene expression profile of term placental environment from T. cruzi seropositive (SP) and seronegative (SN) mothers. Methods. A RNA-Seq was performed in 9 pools of 2 different placental RNA samples each: 3 belonging to placentas from SN and 6 from SP. Each pool consisted of a binomial of a female/male newborn and a vaginal/caesarean delivery. None of the newborns resulted infected. Results. Only 42 genes showed a significant fold change between SP and SN groups. Among the down-regulated genes were KISS1 and CGB5. In the up-regulated genes group were: KIF12, HLA-G, PRG2, TAC3, FN1 and ATXN3L. To identify pathways significantly associated with maternal T. cruzi-infection, a gene-set association analysis was implemented. The placental environment transcriptomic profile of SP consisted of an enrichment in immunological genes sets (inflammatory response and lymphocytic activation were over-expressed) whereas numerous biosynthetic processes were down-regulated. Conclusions. It is worth noting that several differentially expressed genes in SP placentas code for proteins associated to preeclampsia and miscarriage. This first transcriptomics study in human term placental environment from non-infected deliveries shows a placental response that may affect the faetus while protecting it from the parasite infection; this host response could be responsible for the low rate of congenital transmission observed in human chronic Chagas disease. Overall design: Serodiagnosis of pregnant women was done by means of conventional serological methods and carried out by the respective health centres based on routine assays. In maternal and umbilical cord blood samples T. cruzi presence was tested using multiplex Real Time PCR as previously described [6]. Maternal infection with other pathogens that produce congenital transmission and adverse pregnancy outcome were considered as exclusion criteria, as well as missing data or incorrect sampling. Fresh normal placentas were obtained after labour from vaginal or caesarean deliveries and placed within 24 hours at 4°C. Each placenta was dissected and the middle section [7] at 2 cm distance from the umbilical cord was isolated and placed into RNAlater solution (Applied Biosystems, Foster City, CA). Total RNA was extracted with TRIzol reagent (Invitrogen, Carlsbad, CA) and stored at -80°C until used. Transcriptomic studies. A RNA-Seq experiment was done in 9 pools of 2 different placental RNA samples each: 3 pools (C1, C2 and C3) belonging to placentas from seronegative mothers (SN) and 6 pools (TC4 to TC9) from seropositive mothers (SP). Each pool consisted of a binomial of a female/male newborn and a vaginal/caesarean delivery. The cDNA Libraries were prepared according to Illumina''s TruSeq Stranded Total RNA with Ribo-Zero Gold for Human and a Hiseq 2.500 Illumina platform with 100 bp paired-end reads was used for sequencing
Alterations in Placental Gene Expression of Pregnant Women with Chronic Chagas Disease.
Subject
View SamplesJuvenile myelomonocytic leukemia (JMML) is a very rare and aggressive stem cell disease that mainly occurs in young children. RAS activation constitutes the core component of oncogenic signaling. In addition, the leukemic blasts of a quarter of JMML patients present with monosomy 7 (-7), whereas more than half of the patients show enhanced age-adjusted fetal hemoglobin (HbF) levels. Hematopoietic stem cell transplantation is the current standard of care. This results in an event-free survival of 50 - 60%, indicating that novel molecular driven therapeutic options are urgently needed. Using gene expression profiling in an extensive series of 82 patient samples, we aimed at understanding the molecular biology behind JMML and identified a previously unrecognized molecular subgroup characterized by high LIN28B expression.
LIN28B overexpression defines a novel fetal-like subgroup of juvenile myelomonocytic leukemia.
Disease
View SamplesA "Cartes d'Identite des Tumeurs" (CIT) project from the french Ligue Nationale Contre le Cancer (<a href="http://cit.ligue-cancer.net" target="_blank">http://cit.ligue-cancer.net</a>). 104 samples; Affymetrix U133A micro-arrays.<br></br> <br></br> Ninety two patients with T-ALL were diagnosed and treated at Saint-Louis hospital, Paris. Seven patients were studied at diagnosis and relapse (total 99 T-ALL samples). There were 56 children (median age 9 years old; range 1 to 16), and 36 adults (median age 27; range 17 to 66). Informed consent was obtained from the patients and/or relatives. T-ALL diagnosis was based on morphological and immunophenotypical criteria using flow cytometry and an extended monoclonal antibody panel.<br></br> <br></br> Using a combination of molecular cytogenetic and large-scale expression analysis in human T-ALL, we identified and characterized a new recurrent chromosomal translocation, targeting the major homeobox gene cluster HOXA and the TCRB locus. Specific quantitative PCR analysis showed that the expression of the whole HOXA gene cluster was dramatically dysregulated in the HOXA-rearranged cases, and also in MLL and CALM-AF10-related T-ALL cases, strongly suggesting that HOXA genes are oncogenic in these leukemias. Inclusion of HOXA-translocated cases in a general molecular portrait of 92 T-ALL based on large-scale expression analysis shows that this rearrangement defines a new homogeneous subgroup, which shares common biological networks with the TLX1 and TLX3-related cases. Since T-ALLs derive from T-cell progenitors, expression profiles of the distinct T-ALL subgroups were analyzed with respect to those of normal human thymic sub-populations. Inappropriate utilization or perturbation of specific molecular networks involved in thymic differentiation was detected. Moreover, we found a significant association between T-ALL oncogenic subgroups and ectopic expression of a limited set of genes, including several developmental genes, namely HOXA, TLX1, TLX3, NKX3-1, SIX6 and TFAP2C. These data strongly support the view that the abnormal expression of developmental genes, including the prototypical homeobox genes HOXA, is critical in T-ALL oncogenesis.<br></br> <br></br> Project Leader: <br></br> FranC'ois Sigaux<br></br> Institut Universitaire d'Hematologie<br></br> Hopital Saint Louis, Paris, France<br></br> <br></br> Data submission:<br></br>Fabien Petel
HOXA genes are included in genetic and biologic networks defining human acute T-cell leukemia (T-ALL).
Sex, Age, Specimen part, Disease, Disease stage, Subject
View SamplesFull title: Altered levels of MOF (member of MYST family histone acetyl transferase) and decreased levels of H4K16ac correlate with a defective DNA damage response (DDR).
MOF and histone H4 acetylation at lysine 16 are critical for DNA damage response and double-strand break repair.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Conserved molecular interactions within the HBO1 acetyltransferase complexes regulate cell proliferation.
Specimen part, Cell line, Treatment
View SamplesWe find that 499 genes are up-regulated and 457 are down-regulated in response to over-expression of JADE1, while 397 genes are up-regulated and 385 are down-regulated after HBO1 knock-down.
Conserved molecular interactions within the HBO1 acetyltransferase complexes regulate cell proliferation.
Cell line, Treatment
View Samples