This SuperSeries is composed of the SubSeries listed below.
Kruppel-like factor 7 overexpression suppresses hematopoietic stem and progenitor cell function.
Specimen part
View SamplesIncreased expression of Kruppel like factor 7 (KLF7) is an independent predictor of poor outcome in pediatric acute lymphoblastic leukemia. The contribution of KLF7 to hematopoiesis has not been previously described. Herein, we characterized the effect on murine hematopoiesis of the loss of KLF7 and enforced expression of KLF7. Long-term multilineage engraftment of Klf7-/- cells was comparable to control cells, and self-renewal, as assessed by serial transplantation, was not affected. Enforced expression of KLF7 results in a marked suppression of myeloid progenitor cell growth and a loss of short- and long-term repopulating activity. Interestingly, enforced expression of KLF7, while resulting in multi-lineage growth suppression that extended to hematopoietic stem cells and common lymphoid progenitors, spared T cells and enhanced the survival of early thymocytes. RNA expression profiling of KLF7-overexpressing hematopoietic progenitors identified several potential target genes mediating these effects. Notably, the known KLF7 target Cdkn1a (p21Cip1/Waf1) was not induced by KLF7, and loss of CDKN1A does not rescue the repopulating defect. These results suggest that KLF7 is not required for normal hematopoietic stem and progenitor (HSPC) function, but increased expression, as seen in a subset of lymphoid leukemia, inhibits myeloid cell proliferation and promotes early thymocyte survival.
Kruppel-like factor 7 overexpression suppresses hematopoietic stem and progenitor cell function.
Specimen part
View SamplesIncreased expression of Kruppel like factor 7 (KLF7) is an independent predictor of poor outcome in pediatric acute lymphoblastic leukemia. The contribution of KLF7 to hematopoiesis has not been previously described. Herein, we characterized the effect on murine hematopoiesis of the loss of KLF7 and enforced expression of KLF7. Long-term multilineage engraftment of Klf7-/- cells was comparable to control cells, and self-renewal, as assessed by serial transplantation, was not affected. Enforced expression of KLF7 results in a marked suppression of myeloid progenitor cell growth and a loss of short- and long-term repopulating activity. Interestingly, enforced expression of KLF7, while resulting in multi-lineage growth suppression that extended to hematopoietic stem cells and common lymphoid progenitors, spared T cells and enhanced the survival of early thymocytes. RNA expression profiling of KLF7-overexpressing hematopoietic progenitors identified several potential target genes mediating these effects. Notably, the known KLF7 target Cdkn1a (p21Cip1/Waf1) was not induced by KLF7, and loss of CDKN1A does not rescue the repopulating defect. These results suggest that KLF7 is not required for normal hematopoietic stem and progenitor (HSPC) function, but increased expression, as seen in a subset of lymphoid leukemia, inhibits myeloid cell proliferation and promotes early thymocyte survival.
Kruppel-like factor 7 overexpression suppresses hematopoietic stem and progenitor cell function.
Specimen part
View SamplesIncreased expression of Kruppel like factor 7 (KLF7) is an independent predictor of poor outcome in pediatric acute lymphoblastic leukemia. The contribution of KLF7 to hematopoiesis has not been previously described. Herein, we characterized the effect on murine hematopoiesis of the loss of KLF7 and enforced expression of KLF7. Long-term multilineage engraftment of Klf7-/- cells was comparable to control cells, and self-renewal, as assessed by serial transplantation, was not affected. Enforced expression of KLF7 results in a marked suppression of myeloid progenitor cell growth and a loss of short- and long-term repopulating activity. Interestingly, enforced expression of KLF7, while resulting in multi-lineage growth suppression that extended to hematopoietic stem cells and common lymphoid progenitors, spared T cells and enhanced the survival of early thymocytes. RNA expression profiling of KLF7-overexpressing hematopoietic progenitors identified several potential target genes mediating these effects. Notably, the known KLF7 target Cdkn1a (p21Cip1/Waf1) was not induced by KLF7, and loss of CDKN1A does not rescue the repopulating defect. These results suggest that KLF7 is not required for normal hematopoietic stem and progenitor (HSPC) function, but increased expression, as seen in a subset of lymphoid leukemia, inhibits myeloid cell proliferation and promotes early thymocyte survival.
Kruppel-like factor 7 overexpression suppresses hematopoietic stem and progenitor cell function.
Specimen part
View SamplesThe epigenetic changes of the chromatin represent an attractive molecular substrate for adaptation to the environment. We examined here the role of CBP, a histone acetyltransferase involved in mental retardation, in the genesis and maintenance of long-lasting systemic and behavioral adaptations to environmental enrichment (EE). Morphological and behavioral analyses demonstrated that EE ameliorates deficits associated to CBP-deficiency. However, CBP-deficient mice also showed a strong defect in environment-induced neurogenesis and impaired EE-enhanced spatial navigation and patter separation ability. These defects correlated with an attenuation of the transcriptional program induced in response to EE and with deficits in histone acetylation at the promoters of EE-regulated, neurogenesis-related genes. Additional experiments in CBP restricted and inducible knockout mice indicated that environment-induced adult neurogenesis is extrinsically regulated by CBP function in mature granule cells. Overall, our experiments demonstrate that the environment alters gene expression by impinging on activities involved in modifying the epigenome and identify CBP-dependent transcriptional neuroadaptation as an important mediator of EE-induced benefits, a finding with important implications for mental retardation therapeutics.
CBP is required for environmental enrichment-induced neurogenesis and cognitive enhancement.
Sex, Age, Specimen part
View SamplesBackground: Patients with locally advanced or recurrent prostate cancer typically undergo androgen deprivation therapy (ADT), but the benefits are often short-lived, and responses are variable. ADT failure results in castration-resistant prostate cancer (CRPC), that inevitably leads to metastasis. We hypothesized that differences in tumor transcriptional programs may reflect differential responses to ADT and subsequent metastasis. Results: We performed whole transcriptome analysis of 20 patient-matched Pre-ADT biopsies and 20 Post-ADT prostatectomy specimens, and identified two subgroups of patients (high impact and low impact groups) that exhibited distinct transcriptional changes in response to ADT. We found that all patients lost AR-dependent subtype (PCS2) transcriptional signatures. The high impact group maintained the more aggressive subtype (PCS1) signal, while the low impact group more resembled an AR-suppressed (PCS3) subtype. Computational analyses identified transcription factor coordinated groups (TFCGs) enriched in the high impact group network. Leveraging a large public dataset of over 800 metastatic and primary samples, we identified 33 TFCGs in common between high impact group and metastatic lesions, including SOX4/FOXA2/GATA4, ERF/ETV5/ETV3/ELF4, and a TFCG containing JUN, JUNB, JUND, FOS, FOSB, and FOSL1. The majority of metastatic TFCGs were subsets of larger TFCGs in the high impact group network, suggesting refinement of critical TFCGs in prostate cancer progression. Conclusions: We have identified TFCGs associated with pronounced initial transcriptional response to ADT, aggressive signatures, and metastasis. Our findings suggest multiple new hypotheses that could lead to novel combination therapies to prevent development of CRPC following ADT. Overall design: Sequence alignment and gene level expression quantifications were obtained using the STAR read aligner. We obtained an average of 91,077,364 reads (sd: 41,923,139) with a mean transcriptome coverage of 64x (83% mapping to exons).
Identification of the Transcription Factor Relationships Associated with Androgen Deprivation Therapy Response and Metastatic Progression in Prostate Cancer.
Disease, Treatment, Race, Subject
View SamplesAlloplasmic lines provide a unique tool to study the nucleo-cytoplasmic interactions. Alloplasmic lines T183 and T195 were developed through the introgression of the cytoplasm from Aegilops uniaristata (T183) and Aegilops squarrosa (T195) in the nuclear background of Triticum aestivum cv. Chris. Alloplasmic line TH237 was produced introgressing the Hordeum chilense accession H7 cytoplasm into the nuclear background of Triticum aestivum accession T20. Fifty seeds for each sample in pots of 11 cm diameter and grown in controlled conditions under 600E m-2 s1 high light intensity in a daily regime of 12 h light at 22C and 12 h darkness at 15C. Plants were bulked from each pot and three biological replicate used for the transcriptomics Fully expanded second leaves were collected two weeks from sowing in the middle of the light period and used for transcriptomic analysis.
Cytoplasmic genome substitution in wheat affects the nuclear-cytoplasmic cross-talk leading to transcript and metabolite alterations.
Specimen part
View SamplesGene expression analysis of purified KitL-tomato+ and KitL-tomato- thymic vascular endothelial cells, cortical and medullary thymic epithelial cells from 5 weeks old male kitL-tomato reporter mice Overall design: Differentially expressed genes analysis of thymic stromal cells
A dynamic niche provides Kit ligand in a stage-specific manner to the earliest thymocyte progenitors.
No sample metadata fields
View SamplesSingle cell whole transcriptome analysis of young (2-3 months) and old (20-25 months) mouse HSCs, defined as Lin–Sca-1+c-Kit+150+CD48– . Overall design: Differential gene expression analysis of young and old mouse HSCs (Lin–Sca-1+c-Kit+150+CD48– )
Single-cell RNA sequencing reveals molecular and functional platelet bias of aged haematopoietic stem cells.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Comparative genomic evidence for the involvement of schizophrenia risk genes in antipsychotic effects.
Specimen part, Treatment
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