Goal of this study was to assess the levels of protection and investigate cellular, humoral, and mucosal immune correlates on the functional and gene transcriptional levels in elite-controller macaques following high dose SIV challenge.
Rapid SIV Env-specific mucosal and serum antibody induction augments cellular immunity in protecting immunized, elite-controller macaques against high dose heterologous SIV challenge.
Specimen part
View SamplesThe homeobox containing gene Arx is expressed during ventral telencephalon development and it is required for correct GABAergic interneuron tangential migration from the ganglionic eminences to the olfactory bulbs, cerebral cortex and striatum. Its human ortholog is associated with a variety of neurological clinical manifestations whose syntoms are compatible with a loss of cortical interneurons and altered basal ganglia related-activities in humans. Herein, we reported the identification by global expression profiling of a group of genes whose expression is consistently altered in Arx mutant ganglionic eminences. Following analysis revealed the striking ectopic expression in the ganglionic eminences of a number of genes normally not, or only marginally, expressed in the ventral telencephalon. Among them, we functionally analyzed Ebf3, whose ectopic expression in ventral telencephalon is preventingneuronal tangential migration. Further, we showed that Arx is sufficient to repress Ebf3 endogenous expression and that its silencing in Arx mutant tissue might marginally rescue tangential cell movements. Together, these data provide an initial analysis of the molecular pathways regulated by Arx and how their networking might regulate those specific cellular processes during telencephalon development strongly altered by loss of Arx.
Arx acts as a regional key selector gene in the ventral telencephalon mainly through its transcriptional repression activity.
No sample metadata fields
View SamplesAQM shows acute muscle wasting and weakness. Key aspects of AQM include muscle atrophy and myofilament loss. Gene expression profiling, using muscle biopsies from AQM, neurogenic atrophy and normal controls, showed that both myogenic and neurogenic atrophy share induction of myofiber-specific ubiquitin/proteosome pathways while only the AQM shows a specific strong induction of transforming growth factor (TGF)-beta/MAPK pathways.
Constitutive activation of MAPK cascade in acute quadriplegic myopathy.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The Tbr2 Molecular Network Controls Cortical Neuronal Differentiation Through Complementary Genetic and Epigenetic Pathways.
Specimen part
View SamplesThe abscence of TBR2 gene in human leads to microcephaly. This condition is mimicked by the specific ablation of the murine gene in developing cerebral cortex. Herein we compared gene expression in control and Tbr2 cKO in E14.5 cerebral cortices. This approach represents a useful tool to identify the molecular mechanisms at the basis of the phenotype.
The Tbr2 Molecular Network Controls Cortical Neuronal Differentiation Through Complementary Genetic and Epigenetic Pathways.
Specimen part
View SamplesSoft tissue sarcomas are a diverse set of fatal human tumors where few agents have demonstrable clinical efficacy, with the standard therapeutic combination of doxorubicin and ifosfamide showing only a 25-30% response rate in large multi-institutional trials. Although liposarcomas are the most common histological form of adult soft tissue sarcomas, research in this area is severely hampered by the lack of experimentally tractable in vitro model systems. To this end, here we describe a novel in vitro model for human pleomorphic liposarcoma. The cell line (LS2) is derived from a pleomorphic liposarcoma that utilizes Alternative Lengthening of Telomeres (ALT) mechanism of telomere maintenance, which may be particularly important in modulating the response of this tumor type to DNA damaging agents. We present detailed baseline molecular and genomic data, including genome wide copy number and transcriptome profiles, for this model compared to its parental tumor and a panel of liposarcomas covering multiple histologies. The model has retained essentially all of the detectable alterations in copy number that are seen in the parental tumor, and shows molecular karyotypic and expression profiles consistent with pleomorphic liposarcomas. We also demonstrate the utility of this model, together with two additional human liposarcoma cell lines, to investigate the relationship between topoisomerase 2A expression and the sensitivity of ALT-positive liposarcomas to doxorubicin. This model, together with its associated baseline data, provide a powerful new tool to develop treatments for this clinically poorly-tractable tumor, and to investigate the contribution that ALT makes to modulating sensitivity to DNA damaging chemotherapeutic agents such as doxorubicin.
Doxorubicin resistance in a novel in vitro model of human pleomorphic liposarcoma associated with alternative lengthening of telomeres.
Cell line
View SamplesA gene expression signature purporting to distinguish between telomerase and ALT immortalization has recently been described (Lafferty-Whyte et al., 2009). This was obtained as the intersection of two independent signatures, one obtained from cell lines and the other from a panel of liposarcomas, which utilize different telomere maintenance mechanisms (TMMs). To assess the utility of this signature we used Affymetrix U133plus2.0 arrays to undertake a similar analysis of an independent collection of liposarcomas of defined TMM. In our dataset, the 297 gene signature causes the liposarcomas to cluster not on the basis of TMM, but rather on the basis of tumor histological subtype [Figure 1], consistent with the signatures reported by others (Matushansky et al., 2008).
Validating a gene expression signature proposed to differentiate liposarcomas that use different telomere maintenance mechanisms.
No sample metadata fields
View SamplesMyeloproliferative neoplasms are frequently associated with aberrant constitutive tyrosine kinase (TK) activity resulting from point mutations or chimaeric fusion genes, such as BCR ABL1 or JAK2 V617F. We report here for the first time in hematological malignancies, two novel fusion genes involving the TK RET, BCR-RET and FGFR1OP-RET, in chronic myelo monocytic leukemia (CMML) cases. The two RET fusion genes lead to the aberrant activation of RET, are able to transform hematopoietic cells and skew the hematopoietic differentiation program towards the monocytic/macrophage lineage. We also report that the BCR-RET fusion protein is insensitive to Imatinib but sensitive to Sorafenib in vivo. CMML is an hematopoietic malignancy associated with the frequent activation of the RAS pathway. The RET fusion genes seems to constitutively mimic the same signaling pathway than RAS mutations. Overall, the RET fusion genes behaviors in the monocytic lineage underlie the role of the normal RET TK activity during the physiological monocytic differentiation.
RET fusion genes are associated with chronic myelomonocytic leukemia and enhance monocytic differentiation.
Cell line
View SamplesDirect cell reprogramming has enabled the direct conversion of skin fibroblasts into functional neurons and oligodendrocytes using a minimal set of cell lineage-specific transcription factors. This approach has substantial advantages since it is rapid and simple, generating the cell type of interest in a single step. However, it remains unknown whether this technology can be applied for directly reprogramming skin cells into astrocytes, the third neural lineage. Astrocytes play crucial roles in neuronal homeostasis and their dysfunctions contribute to the origin and progression of multiple human diseases. Herein, we carried out a screening using several transcription factors involved in defining the astroglial cell fate and identified NFIA, NFIB and SOX9 to be sufficient to convert with high efficiency embryonic and post-natal mouse fibroblasts into astrocytes (iAstrocytes). We proved both by gene expression profiling and functional tests that iAstrocytes are comparable to native brain astrocytes. This protocol can be then employed to generate functional iAstrocytes for a wide range of experimental applications.
Direct conversion of fibroblasts into functional astrocytes by defined transcription factors.
Specimen part
View SamplesAnalysis of estrogen receptor (ER)-positive MCF7 cell total RNA expression and polysome-assiciated RNA expression following treatment with estradiol (E2) and vehicle (etoh).
Estrogen coordinates translation and transcription, revealing a role for NRSF in human breast cancer cells.
Cell line
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