Project description:Mammals differ more than 100-fold in maximum lifespan. Here, we conducted comparative transcriptomics on 26 species with diverse lifespans. We identified thousands of genes with expression levels negatively or positively correlated with a species' maximum lifespan (Neg- or Pos-MLS genes). Neg-MLS genes are primarily involved in energy metabolism and inflammation. Pos-MLS genes show enrichment in DNA repair, microtubule organization, and RNA transport. Expression of Neg- and Pos-MLS genes is modulated by interventions, including mTOR and PI3K inhibition. Regulatory networks analysis showed that Neg-MLS genes are under circadian regulation possibly to avoid persistent high expression, whereas Pos-MLS genes are targets of master pluripotency regulators OCT4 and NANOG and are upregulated during somatic cell reprogramming. Pos-MLS genes are highly expressed during embryogenesis but significantly downregulated after birth. This work provides targets for anti-aging interventions by defining pathways correlating with longevity across mammals and uncovering circadian and pluripotency networks as central regulators of longevity.
Project description:Using Gfi1b conditional mice, deletion of gfi1b in the hematopietic system was induced by injecting MxCre tg Gfi1bfl/fl mice with pIpC. 30 days after injection, Cd150 pos, Cd 48 neg, Lin neg Sca and c-kit pos stem cells were sortrted from Gfi1bfl/fl and Mxcre tg Gfi1bfl/fl mice and analysed. We used the mouse Affymetrix Gene ST Array.
Project description:We sorted Group 3 MB xenografts tumors by PRTG surface expression and performed single-cell RNA sequencing on the PRTG-pos and PRTG-neg fractions.
Project description:Using Gfi1b conditional mice, deletion of gfi1b in the hematopietic system was induced by injecting MxCre tg Gfi1bfl/fl mice with pIpC. 30 days after injection, Cd150 pos, Cd 48 neg, Lin neg Sca and c-kit pos stem cells were sortrted from Gfi1bfl/fl and Mxcre tg Gfi1bfl/fl mice and analysed. We used the mouse Affymetrix Gene ST Array. The study should determine whether loss of Gfi1 alters the gene expression pattern in the hematopietic stem cells.
Project description:Human engineered CRC organoids were equipped with the intestinal stem cell reporter STAR reflecting transcriptional activity of ASCL2. Successfully growing organoids display heterogeneous STAR expression and grow into big structures, while growth-compromised organoids stay small and are either entirely STAR-pos or STAR-neg.
Project description:Here we present MS1 spectra of nontoxigenic and toxigenic BF cells membrane extract, complemented by MS/MS spectra of separate parent ions in positive and negative mode
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MS1 total spectra BFplus and BFminus in negative and positive mode
2015-09-04-pos-bminus-baselinel-1.d - MS1 acquisition spectre of sample BFminus in pos mode, sample acquisition started from 7.5 min of chromatogramm
2015-09-04-pos-bminus-picture-tertac-dla lockmass.d - MS1 acquisition spectre of sample BFminus in pos mode, tetracycline as internal standard was used,m/z 445
NAT-neg-6-plus.d - MS1 acquisition spectre of sample BFplus in neg mode
nat-plus-pos.d- MS1 acquisition spectre of sample BFplus in pos mode
NAT-neg-2-minus-1-10.d - MS1 acquisition spectre of sample BFminus in neg mode
Project description:Eighteen independent neurospheres derived from patients affected by primary glioblastoma were grouped into “classical”, “mesenchymal” or “proneural” subtypes according to analysis of genetic lesions and gene expression profiling. Here we show that expression of the MET oncogene, encoding the tyrosine kinase receptor for HGF, associates with mesenchymal and proneural neurospheres (Met-pos-NS). Met expression is almost absent from classical neurospheres (Met-neg-NS), and mutually exclusive with amplification and expression of the EGF receptor gene. Met-pos-NS and Met-neg-NS display distinct growth factor requirements, differentiate along divergent pathways, and generate tumors with distinctive histological features. Met-pos-NS contain a variable percentage of Met positive (Methigh) and Met negative (Metneg) cells. After purification, only Methigh cells display clonogenic ability in vitro, and regenerate neurospheres containing both Methigh and Metneg cells. After in vivo transplantation, Methigh cells display highly enriched tumorigenic potential as compared with Metneg cells. At functional level, in Methigh cells, HGF concomitantly sustains proliferation, clonogenicity, expression of self-renewal markers, migration and invasion. These data show that Met is a functional marker of glioblastoma stem cells, and a candidate target for molecular diagnosis and therapy of a glioblastoma subset.
Project description:The transcription co-factor FOG1 interacts with the chromatin remodeling complex NuRD to mediate gene activation and gene repression during hematopoiesis. We have generated mice with a targeted mutation in the endogenous Fog1 locus that results in an N-ternimal mutation in FOG1 that disrupts the interaction with NuRD. We used gene expression microarrays to explore the global transcriptional programs regulated by FOG1 and NuRD in megakaryocyte-erythroid progenitors (MEP) to aid in understanding its role during hematopoiesis. Flow cytometry was used to isolate Megakaryocyte-Erythroid progenitors (MEP) from murine bone marrow. MEP were identified as Lineage neg, kit pos, Sca1 neg, CD34 neg, FcgrII/III low cells.
Project description:Eighteen independent neurospheres derived from patients affected by primary glioblastoma were grouped into “classical”, “mesenchymal” or “proneural” subtypes according to analysis of genetic lesions and gene expression profiling. Here we show that expression of the MET oncogene, encoding the tyrosine kinase receptor for HGF, associates with mesenchymal and proneural neurospheres (Met-pos-NS). Met expression is almost absent from classical neurospheres (Met-neg-NS), and mutually exclusive with amplification and expression of the EGF receptor gene. Met-pos-NS and Met-neg-NS display distinct growth factor requirements, differentiate along divergent pathways, and generate tumors with distinctive histological features. Met-pos-NS contain a variable percentage of Met positive (Methigh) and Met negative (Metneg) cells. After purification, only Methigh cells display clonogenic ability in vitro, and regenerate neurospheres containing both Methigh and Metneg cells. After in vivo transplantation, Methigh cells display highly enriched tumorigenic potential as compared with Metneg cells. At functional level, in Methigh cells, HGF concomitantly sustains proliferation, clonogenicity, expression of self-renewal markers, migration and invasion. These data show that Met is a functional marker of glioblastoma stem cells, and a candidate target for molecular diagnosis and therapy of a glioblastoma subset. 37 samples (17 replicate samples and 1 triplicate sample)