In addition to its well-know function in chromosome segregation, increasing evidence implicates cohesin in the control of gene expression. It has been previously reported that inactivation of the cohesin loader Mis4 in G1-arrested cells leads to the dissociation of cohesin from chromatin. We exploited this experimental situation to ask whether this loss of cohesin would affect gene expression on a genome-wide scale.
Role for cohesin in the formation of a heterochromatic domain at fission yeast subtelomeres.
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View SamplesPatient-derived xenograft models are considered to represent the heterogeneity of human cancers and might be more relevant preclinical models to evaluate effective therapeutic agents. Our consortium joins efforts to extensively develop and characterize a new collection of patient-derived colorectal cancer models. From 86 unsupervised surgical colon sample collection, 54 tumors were successfully xenografted in immunodeficient mice and rats, representing 35 primary tumors, 5 peritoneal carcinosis and 14 metastases. Our histological and molecular characterization of patient tumors, first passage on mice and later passages includes the sequence of key genes involved in CRC (ie APC, KRAS, TP53), CGH array and transcriptomic analysis. This comprehensive characterization demonstrates that our collection recapitulates the clinical situation regarding the histopathological and molecular diversity of colorectal cancers. Moreover, patient tumors and corresponding models are clustering together which gives the opportunity to look for relevant signatures and comparison studies between clinical and preclinical data. Hence, we performed pharmacological monotherapy studies with standard of care for colon cancer (5-FU, oxaliplatin, irinotecan, cetuximab). Through this extensive in vivo analysis, we have compared the molecular profile with the drug sensitivity of each tumor models, and run an equivalent of a cetuximab phase II clinical trial in a preclinical setting. Our results confirm the key role of KRAS mutation in the cetuximab resistance and demonstrate that such collection could bring benefit to evaluate novel targeted therapeutic strategies and potentially help the stratification strategy for cancer patients according to molecular marker. This set correspond to 82 CGH profiles, with 7 samples from patient tumor and 75 samples from mouse xenograft at different passages P0 to P9. All hybridizations are performed with Human CGH 244K Agilent arrays (amadid 014693) in dual color with Human DNA Promega (sex matched) as reference. ID for biosources without an -Px suffix correspond to tumor patients. ID with a suffix correspond to xenograft with 0 for the first passage.
Characterization of a large panel of patient-derived tumor xenografts representing the clinical heterogeneity of human colorectal cancer.
Specimen part, Disease, Disease stage, Time
View SamplesLiving organisms have to cope with multiple and combined fluctuations in their environment. According to their sessile mode of life, plants are even more subjected to such fluctuations impacting their physiology and development. In particular, nutrient availability is known to tune plant development through modulating hormonal signaling, and conversely, hormonal signals are key to control nutrient related signaling pathways (Krouk et al., 2011a). However, very few is known about molecular mechanisms leading to plant adaptation to such combined signals. Here we deployed an unprecedented combinatorial treatment matrix to reveal plant adaptation in response to nitrate (NO3-), ammonium (NH4+), auxin (IAA), cytokinins (CK) and abscisic acid (ABA) and their exhaustive binary combinations.
Combinatorial interaction network of transcriptomic and phenotypic responses to nitrogen and hormones in the Arabidopsis thaliana root.
Specimen part, Time
View SamplesC57Bl6J mice were injected CCL4 for 8 weeks to induce liver injury and livers were used to prepare RNA.
Interspecies NASH disease activity whole-genome profiling identifies a fibrogenic role of PPARα-regulated dermatopontin.
Sex, Specimen part, Treatment
View SamplesThis work uses a time series in order to decipher gene relationships and consequently to build core regulatory networks involved in Arabidopsis root adaptation to NO3- provision. The experimental approach has been to monitor genome response to NO3- at 3, 6, 9, 12, 15 and 20 min, using ATH1 chips. This high-resolution time course analysis demonstrated that the previously known primary nitrate response is actually preceded by very fast (within 3 min) gene expression modulation, involving genes/functions needed to prepare plants to use/reduce NO3-. State-space modeling (a machine learning approach) has been used to successfully predict gene behavior in unlearnt conditions.
Predictive network modeling of the high-resolution dynamic plant transcriptome in response to nitrate.
Specimen part, Treatment
View SamplesWe used Affymetrix microarrays to detail the global programme of gene expression regulated by CBP and/or p300 during human primary myoblast differentiation.
No associated publication
Specimen part, Subject, Time
View SamplesIn this study, we sought to identify the mRNAs associated to FMRP protein in mouse cortical neuron using a cross linking immunoprecipitation and microarray (CLIP-microarray).
Fragile X Mental Retardation Protein (FMRP) controls diacylglycerol kinase activity in neurons.
Specimen part
View SamplesNRT1.1 is a nitrate transceptor involved in many nitrate responses including the regulation of gene expression through (i) the Primary Nitrate Response (PNR) and (ii) the regulation the NRT2.1 gene under continuous high NH4NO3 conditions. Phosphorylation of NRT1.1s T101 residue is involved in the modulation of the PNR whereas nitrate transport by NRT1.1 is not. Here we used various NRT1.1 point mutants to study the impact of NRT1.1 on the whole transcriptome under high NH4NO3 supply. Col is the WT control, chl1-5 and chl1-12 are KO mutants, chl1-9 is defective in nitrate transport but not in PNR induction, T101D and T101A mimick the phosphorylated and not phosphorylated forms of NRT1.1 respectively.
No associated publication
Specimen part
View SamplesHematopoietic progenitor and stem cells from bone marrow have been sorted by FACS (LSK, Lineage -, Sca1 + and cKit +) and co-culture during 18h without cytokines with or without extracellular vesicles (EV) secreted by AFT stromal cells.
Extracellular vesicles of stromal origin target and support hematopoietic stem and progenitor cells.
Specimen part
View SamplesLivers from wild-type (WT) or Ppara knock-out (Ppara KO) C57Bl6 mice were used to prepare RNA which was then processed for analysis using MoGene-2_0-st Affymetrix microarrays according to standard procedures.
The logic of transcriptional regulator recruitment architecture at <i>cis</i>-regulatory modules controlling liver functions.
Sex, Specimen part
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