Acute myeloid leukemia (AML) is a heterogeneous group of malignancies which may be sensitive to the natural killer (NK) cell anti-tumor response. However, NK cells are frequently defective in AML. Here, we found in an exploratory cohort (n = 46) that NK-cell status at diagnosis of AML separated patients in two groups with a different clinical outcome. Patients with a deficient NK-cell profile, including reduced expression of some activating NK receptors (e.g. DNAM-1, NKp46 and NKG2D) and decreased IFN-g production, had a significantly higher risk of relapse (P = 0.03) independently of cytogenetic classification in multivariate analysis. Patients with defective NK cells showed a profound gene expression decrease in AML blasts for cytokine and chemokine signaling (e.g. IL15, IFNGR1, IFNGR2, CXCR4), antigen processing (e.g. HLA-DRA, HLA-DRB1, CD74) and adhesion molecule pathways (e.g. PVR, ICAM1). A set of 388 leukemic classifier genes defined in the exploratory cohort was independently validated in a multicentric cohort of 194 AML patients. In total, these data evidenced the interplay between NK-cells and AML blasts at diagnosis allowing an immune-based stratification of AML patients independently of clinical classifications.
Defective NK Cells in Acute Myeloid Leukemia Patients at Diagnosis Are Associated with Blast Transcriptional Signatures of Immune Evasion.
Disease, Subject
View SamplesAcute myeloid leukemia (AML) is a heterogeneous group of malignancies which may be sensitive to the natural killer (NK) cell anti-tumor response. However, NK cells are frequently defective in AML. Here, we found in an exploratory cohort (n = 46) that NK-cell status at diagnosis of AML separated patients in two groups with a different clinical outcome. Patients with a deficient NK-cell profile, including reduced expression of some activating NK receptors (e.g. DNAM-1, NKp46 and NKG2D) and decreased IFN-g production, had a significantly higher risk of relapse (P = 0.03) independently of cytogenetic classification in multivariate analysis. Patients with defective NK cells showed a profound gene expression decrease in AML blasts for cytokine and chemokine signaling (e.g. IL15, IFNGR1, IFNGR2, CXCR4), antigen processing (e.g. HLA-DRA, HLA-DRB1, CD74) and adhesion molecule pathways (e.g. PVR, ICAM1). A set of 388 leukemic classifier genes defined in the exploratory cohort was independently validated in a multicentric cohort of 194 AML patients. In total, these data evidenced the interplay between NK-cells and AML blasts at diagnosis allowing an immune-based stratification of AML patients independently of clinical classifications.
Defective NK Cells in Acute Myeloid Leukemia Patients at Diagnosis Are Associated with Blast Transcriptional Signatures of Immune Evasion.
Age, Disease, Disease stage
View SamplesWe used whole genome transcriptome as gene discovery to dissect the developmental organization of human lymphopoiesis.
Molecular and Functional Characterization of Lymphoid Progenitor Subsets Reveals a Bipartite Architecture of Human Lymphopoiesis.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The activity-dependent histone variant H2BE modulates the life span of olfactory neurons.
Sex, Age, Specimen part
View SamplesWe have identified a replication-independent histone variant, Hist2h2be (referred to herein as H2be), which is expressed exclusively by olfactory chemosensory neurons. Levels of H2BE are heterogeneous among olfactory neurons, but stereotyped according to the identity of the co-expressed olfactory receptor (OR). Gain- and loss-of-function experiments demonstrate that changes in H2be expression affect olfactory function and OR representation in the adult olfactory epithelium. We show that H2BE expression is reduced by sensory activity and that it promotes neuronal cell death, such that inactive olfactory neurons display higher levels of the variant and shorter life spans. Post-translational modifications (PTMs) of H2BE differ from those of the canonical H2B, consistent with a role for H2BE in altering transcription. We propose a physiological function for H2be in modulating olfactory neuron population dynamics to adapt the OR repertoire to the environment.
The activity-dependent histone variant H2BE modulates the life span of olfactory neurons.
Age, Specimen part
View SamplesGenomic imprinting results in the preferential expression of the paternal, or maternal allele of certain genes. We have performed a genome-wide characterization of imprinting in the mouse embryonic and adult brain using F1 hybrid mice generated from reciprocal crosses of CASTEiJ and C57BL/6J mice. We also uncovered genes associated with sex specific parental effects in the adult mouse brain. Our study identified preferential selection of the maternally inherited X chromosome in glutamatergic neurons of the female cortex. Overall design: Examination of allele specific expression in the brains of reciprocal crosses of F1 hybrid mice from CASTEiJ and C57BL/6J crosses. Processed data files (GenomicAligned, SNP_calls, TranscriptomeAligned, fRNAdbAligned) and README file linked below as supplementary files.
Sex-specific parent-of-origin allelic expression in the mouse brain.
No sample metadata fields
View SamplesWe analyzed Purkinje cell transcriptome dynamics in the developing mouse cerebellum during the first three postnatal weeks, a key developmental period equivalent to the third trimester in human cerebellar development. Our study represents the first detailed analysis of developmental Purkinje cell transcriptomes and provides a valuable dataset for gene network analyses and biological questions on genes implicated in cerebellar and Purkinje cell development. Overall design: Laser capture microdissection was employed to obtain a highly enriched population of cerebellar Purkinje cells. Deep sequencing was performed on RNA isolated from 1000 Purkinje cells at five developmental timepoints (postnatal days P0, P4, P8, P14 and P21) in triplicate.
A gene expression signature in developing Purkinje cells predicts autism and intellectual disability co-morbidity status.
Specimen part, Cell line, Subject
View SamplesWe sought to investigate the scope of cellular and molecular changes within a mouse's olfactory system as a function of its exposure to odors emitted from members of the opposite sex. To this end, we housed mice either separated from members of the opposite sex (sex-separated) or together with members of the opposite sex (sex-combined) until six months of age and then profiled transcript levels within the main olfactory epithelium (MOE), vomeronasal organ (VNO), and olfactory bulb (OB) of the mice via RNA-seq. For each tissue type, we then analyzed gene expression differences between sex-separated males and sex-separated females (SM v SF), sex-combined males and sex-combined females (CM v CF), sex-separated females and sex-combined females (SF v CF), and sex-separated males and sex-combined males (SM v CM). Within both the MOE and VNO, we observed significantly more numerous gene expression differences between males and females when mice were sex-separated as compared to sex-combined. Chemoreceptors were highly enriched among the genes differentially expressed between males and females in sex-separated conditions, and these expression differences were found to reflect differences in the abundance of the corresponding sensory neurons. Overall design: For each combination of tissue (MOE, VNO, OB), sex (F, M), and condition (sex-separated [S], sex-combined [C]), we generated three biological replicate samples of RNA, each of which contained equal quantities of RNA from two different mice. This resulted in a total of 36 samples.
Sex separation induces differences in the olfactory sensory receptor repertoires of male and female mice.
Sex, Age, Cell line, Subject
View SamplesPhospho-ribosome associated RNAs were immunopurified using the antibodies against phospho-S6. The purified RNAs were converted to cDNAs, which were sequenced in Illumina HiSeq platform. Vomeronasal organs were extracted from male CD-1 animals exposed to either pup cues or fresh bedding. Overall design: Total of 6 samples, 2 conditions and 3 replicates
Multisensory Logic of Infant-Directed Aggression by Males.
Sex, Specimen part, Cell line, Subject
View SamplesB6D2F1 male mice at the age of 6 weeks were maintained for one week in a 12h light / 12 h dark (LD12:12) cycle (lights on from 7:00 am to 7:00 pm) and food and water ad libitum. Mice were then divided in two experimental groups which were further maintained for 3 weeks in the LD12 cycle and fed either at libitum or only during a 4 h period between 9:00 am and 1:00 pm. All animals were then implanted subcutaneously with a pancreatic P03 adenocarcinoma in both flanks. Tumour growth was monitored daily and twenty one days after innoculation, animals were transfered to constant darkness for 24h. Tumour samples were collected at the implantation site at circadian time (CT)4 and CT16.
Cancer inhibition through circadian reprogramming of tumor transcriptome with meal timing.
Sex, Age, Specimen part, Time
View Samples