This SuperSeries is composed of the SubSeries listed below.
A post-transcriptional program of chemoresistance by AU-rich elements and TTP in quiescent leukemic cells.
Specimen part, Cell line, Treatment
View SamplesQuiescence (G0) is a transient, cell cycle-arrested state. By entering G0, cancer cells survive unfavorable conditions such as chemotherapy and cause relapse. While G0 cells have been studied at the transcriptome level, how post-transcriptional regulation contributes to their chemoresistance remains unknown. We induced chemoresistant and quiescent (G0) leukemic cells by serum-starvation or chemotherapy treatment. To study post-transcriptional regulation in G0 leukemic cells, we systematically analyzed their transcriptome, translatome, and proteome. We find that our resistant G0 cells recapitulate gene expression profiles of in vivo chemoresistant leukemic and G0 models. In G0 cells, canonical translation initiation is inhibited; yet we find that inflammatory genes are highly translated, indicating alternative post-transcriptional regulation. Importantly, AU-rich elements (AREs) are significantly enriched in the up-regulated G0 translatome and transcriptome. Mechanistically, we find the stress-responsive p38 MAPK-MK2 signaling pathway stabilizes ARE mRNAs by phosphorylation and inactivation of mRNA decay factor, tristetraprolin (TTP) in G0. This permits expression of ARE mRNAs that promote chemoresistance. Conversely, inhibition of TTP phosphorylation by p38 MAPK inhibitors and non-phosphorylatable TTP mutant decreases ARE-bearing TNFα and DUSP1 mRNAs and sensitizes leukemic cells to chemotherapy. Furthermore, co-inhibiting p38 MAPK and TNFα—prior to or along with chemotherapy—substantially reduced chemoresistance in primary leukemic cells ex vivo and in vivo. These studies uncover post-transcriptional regulation underlying chemoresistance in leukemia. Our data reveal the p38 MAPK-MK2-TTP axis as a key regulator of expression of ARE bearing mRNAs that promote chemoresistance. By disrupting this pathway, we developed an effective combination therapy against chemosurvival.
A post-transcriptional program of chemoresistance by AU-rich elements and TTP in quiescent leukemic cells.
Cell line, Treatment
View SamplesQuiescence (G0) is a transient, cell cycle-arrested state. By entering G0, cancer cells survive unfavorable conditions such as chemotherapy and cause relapse. While G0 cells have been studied at the transcriptome level, how post-transcriptional regulation contributes to their chemoresistance remains unknown. We induced chemoresistant and quiescent (G0) leukemic cells by serum-starvation or chemotherapy treatment. To study post-transcriptional regulation in G0 leukemic cells, we systematically analyzed their transcriptome, translatome, and proteome. We find that our resistant G0 cells recapitulate gene expression profiles of in vivo chemoresistant leukemic and G0 models. In G0 cells, canonical translation initiation is inhibited; yet we find that inflammatory genes are highly translated, indicating alternative post-transcriptional regulation. Importantly, AU-rich elements (AREs) are significantly enriched in the up-regulated G0 translatome and transcriptome. Mechanistically, we find the stress-responsive p38 MAPK-MK2 signaling pathway stabilizes ARE mRNAs by phosphorylation and inactivation of mRNA decay factor, tristetraprolin (TTP) in G0. This permits expression of ARE mRNAs that promote chemoresistance. Conversely, inhibition of TTP phosphorylation by p38 MAPK inhibitors and non-phosphorylatable TTP mutant decreases ARE-bearing TNFα and DUSP1 mRNAs and sensitizes leukemic cells to chemotherapy. Furthermore, co-inhibiting p38 MAPK and TNFα—prior to or along with chemotherapy—substantially reduced chemoresistance in primary leukemic cells ex vivo and in vivo. These studies uncover post-transcriptional regulation underlying chemoresistance in leukemia. Our data reveal the p38 MAPK-MK2-TTP axis as a key regulator of expression of ARE bearing mRNAs that promote chemoresistance. By disrupting this pathway, we developed an effective combination therapy against chemosurvival.
A post-transcriptional program of chemoresistance by AU-rich elements and TTP in quiescent leukemic cells.
Specimen part, Treatment
View SamplesThe goal of this study is to elucidate the influence of treadmill training on transcriptome of the upper lumbar spinal cord after thoracic spinal cord hemisection. mRNA profiles of spinal cords at 23 days-post injury with/without treadmill training were generated. The expression levels of 650 genes in the trained animal were increased ( > 2-fold) compared to untrained animals. Our study represents the detailed analysis of transcriptomes of spinal cord distal to the hemisected lesion after treadmill training, with biologic replicates, generated by RNA-seq technology. Overall design: The effect of training after spinal cord injury (T9) on the transcriptome of intact upper spinal cord was investigated.
Locomotor Training Increases Synaptic Structure With High NGL-2 Expression After Spinal Cord Hemisection.
Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Comprehensive developmental profiles of gene activity in regions and subregions of the Arabidopsis seed.
Specimen part
View SamplesWe collected globular stage seed compartments from 5 or 7-micron paraffin sections using the Leica LMD6000 system in order to identify the mRNAs present in different compartments of an Arabidopsis seed containing a globular stage embryo. For the purposes of this study we broke down the seed into 8 capturable compartments: embyro proper, suspensor, micropylar endosperm, peripheral endosperm, chalazal endosperm, chalazal seed coat, general seed coat, and whole seeds.
Comprehensive developmental profiles of gene activity in regions and subregions of the Arabidopsis seed.
No sample metadata fields
View SamplesWe collected heart stage seed compartments from 7 micron paraffin sections using the Leica LMD6000 system in order to identify the mRNAs present in different compartments from seeds containing heart stage embryos. For the purposes of this study we captured 6 compartments: embryo proper, micropylar endosperm, peripheral endosperm, chalazal endosperm, chalazal seed coat and seed coat, as well sets of serial sections encompassing the entire heart stage seed.
Comprehensive developmental profiles of gene activity in regions and subregions of the Arabidopsis seed.
Specimen part
View SamplesWe collected linear-cotyledon stage seed compartments from 5 to 7 micron paraffin sections using the Leica LMD6000 system in order to identify the mRNAs present in different compartments from seeds containing linear-coyledon-stage embryos. For the purposes of this study we captured 7 compartments: embyro proper, cellularized endosperm, chalazal endosperm, chalazal seed coat, general seed coat, whole seeds and micropylar endosperm.
Comprehensive developmental profiles of gene activity in regions and subregions of the Arabidopsis seed.
No sample metadata fields
View SamplesWe collected mature green seed compartments from 7 micron paraffin sections using the Leica LMD6000 system in order to identify the mRNAs present in different compartments from seeds containing mature green-stage embryos. For the purposes of this study we captured 6 compartments: embryo proper, micropylar endosperm, cellularized peripherial endosperm, chalazal endosperm, chalazal seed coat and seed coat, as well sets of serial sections encompassing the entire mature green stage seed.
Comprehensive developmental profiles of gene activity in regions and subregions of the Arabidopsis seed.
Specimen part
View SamplesWe collected pre-globular stage seed compartments from 7-micron paraffin sections using the Leica LMD6000 system in order to identify the mRNAs present in different compartments of seeds containing pre-globular-stage embryos was identified as those seeds containing embryo propers made up of between 2 and 8 cells. For the purposes of this study we captured 6 compartments: embyro proper, micropylar endosperm, peripheral endosperm, chalazal endosperm, chalazal seed coat and general seed coat. Serial sections of entire seeds were also captured for comparison.
Comprehensive developmental profiles of gene activity in regions and subregions of the Arabidopsis seed.
No sample metadata fields
View Samples