Irradiation induced bone marrow ablation ultimately enhanced PTH anabolic effects in bone.
An irradiation-altered bone marrow microenvironment impacts anabolic actions of PTH.
Specimen part, Treatment
View SamplesThe Hedgehog (Hh) signaling pathway is a developmentally conserved regulator of stem cell function. Several reports suggested that Hh signaling is an important regulator of hematopoietic stem cell (HSC) maintenance and differentiation. Here we test this hypothesis in vivo using both gain- and loss-of-function Hh genetic models. Surprisingly, our studies demonstrate that conditional Smoothened (Smo) deletion or over-activation has no significant effects on adult HSC self-renewal and function. Moreover, they indicate a lack of synergism between the Notch and Hh pathways in HSC function, as RBPJ- and Smo-deficiency do not affect hematopoiesis. In agreement with this notion, detailed genome-wide transcriptome analysis reveals that silencing of Hh signaling does not significantly alter the HSC-specific gene expression signature. Our studies demonstrate that the Hh signaling pathway is dispensable for adult HSC function and suggest that the Hh pathway can be targeted in future clinical trials addressing the effect of Hh inhibition on leukemia-initiating cell maintenance.
Hedgehog signaling is dispensable for adult hematopoietic stem cell function.
Sex
View SamplesDissemination of cancer stem cells (CSCs) serves as the basis of metastasis. Recently, we demonstrated that circulating prostate cancer (PCa) targets the hematopoietic stem cell (HSCs) niche in marrow during dissemination. Once in the niche, disseminated tumor cells (DTCs) may remain dormant for extended periods. As the major function of the HSC niche is to maintain stem cell functions, we hypothesized that the niche regulates CSC activities of DTCs. We show that DTCs recovered from marrow were significantly enriched for a CSC phenotype. Critically, the conversion of DTCs to CSCs is regulated by niche. The data demonstrate that the niche plays a significant role in maintaining tumor-initiating PCa in marrow and suggests a functional relationship between CSCs and dormancy. Understanding how the marrow niche regulates the conversion of DTCs to CSCs is critical for the development of therapeutics specifically targeting skeletal bone metastasis and dormancy.
The marrow niche controls the cancer stem cell phenotype of disseminated prostate cancer.
Specimen part
View SamplesTotal RNA microarray data from Fresh-Frozen Glioblastoma tumor samples.
Epigenetic suppression of EGFR signaling in G-CIMP+ glioblastomas.
Specimen part, Disease stage
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome-wide screen of cell-cycle regulators in normal and tumor cells identifies a differential response to nucleosome depletion.
Specimen part, Cell line
View SamplesGene-expression in siRNA treated U2OS and hTERT-RPE1 cells showed that CASP8AP2, NPAT and HINFP do not regulate expression of each other, and do not have any common target genes, except histones. Most histone genes are downregulated in U2OS cells following loss of CASP8AP2, NPAT or HINFP. In normal cells, highly-expressed histone genes were downregulated, albeit less than in tumor cells following loss of CASP8AP2. The p53 target genes were upregulated relatively late, clearly after the changes in expression of histone genes were observed.
Genome-wide screen of cell-cycle regulators in normal and tumor cells identifies a differential response to nucleosome depletion.
Cell line
View SamplesTF binding clusters in promoter correlate well with gene expression. We used ChIP-seq to map binding sites of the majority of highly expressed TFs in the cell. The size of clusters of TFs in the promoters of genes were found to correlate well with gene expression.
Transcription factor binding in human cells occurs in dense clusters formed around cohesin anchor sites.
Cell line
View SamplesGene expression profiles of 10 uterine leiomyomas and their matched normal myometrium specimens were studied using Affymetrix GeneChip Human Genome U133 Plus 2.0 gene expression arrays. Four tumors displayed a codon 44 mutation, four carried a intron 1 mutation, and the remaining two displayed no MED12 mutation.
MED12, the mediator complex subunit 12 gene, is mutated at high frequency in uterine leiomyomas.
Specimen part, Subject
View SamplesTo identify downstream targets of Jak/Stat3 pathways without being distracted by differentiation signalings from MEK/ERK pathway, we exploited a engineered B6 cells, which stably stably expressing a chimeric receptor (GRgp-Y118F). The chimeric receptor can induce the phosphorylation of Stat3 by GCSF without activating the MEK/ERK pathway. To mimic the effect of GCSF, the chimeric B6 cells were also treated with LIF plus a selective MEK chemical inhibitor, PD0325901, to induce LIF/Jak/Stat3 but MEK/ERK pathways.
Gbx2, a LIF/Stat3 target, promotes reprogramming to and retention of the pluripotent ground state.
Cell line
View SamplesAnalysis of ovarian cancer cell lines after knockdown of FGFRL1 using SiRNA.
FGFRL1 Promotes Ovarian Cancer Progression by Crosstalk with Hedgehog Signaling.
Cell line
View Samples