Bmi1 is a component of polycomb repressive complex 1 and its role in the inheritance of the stemness of adult somatic stem cells has been well characterized. Bmi1 maintains the self-renewal capacity of adult stem cells, at least partially, by repressing the Ink4a/Arf locus that encodes a cyclin-dependent kinase inhibitor, p16Ink4a, and a tumor suppressor, p19Arf 14. Deletion of both Ink4a and Arf in Bmi1-deficient mice substantially restored the defective self-renewal capacity of HSCs and neural stem cells.
Poised lineage specification in multipotential hematopoietic stem and progenitor cells by the polycomb protein Bmi1.
Specimen part
View SamplesThe division rate of hematopoietic stem cells (HSCs) are promoted by estradiol. To identify the mechanism by which estradiol regulates HSCs, we performed gene expresssion profiling of HSCs isolated from mice of both sexes treated with either control vehicle (oil) or estradiol for one week.
Oestrogen increases haematopoietic stem-cell self-renewal in females and during pregnancy.
Sex, Specimen part
View SamplesFus is the gene for a member of the FET family of RNA-binding proteins often involved in chromosomal translocations to generate oncogenic fusion genes in human cancers. Fus participates in multiple cellular functions, including RNA processing and transport, transcriptional regulation, and genome integrity. We uncovered its critical role in the maintenance of hematopoietic stem cells (HSCs). Fus-/- fetal livers developed normally except for a mild reduction in numbers of colony-forming cells compared to the wild type. The proliferation and differentiation of Fus-/- hematopoietic progenitors were normal in vitro. However, the number of colony-forming cells present in long-term cocultures of Fus-/- hematopoietic progenitors and stromal cells was significantly reduced. Fus-/- HSCs had an impaired long-term repopulating capacity and failed to repopulate in tertiary recipient mice. Fus-/- HSCs were highly susceptible to radiation both in vitro and in vivo and showed retardation of radiation-induced DNA damage repair. These findings define Fus as a novel regulator of HSCs and implicate it in stress-resistance and maintenance of the genomic integrity of HSCs. Therefore, it would be of importance to analyze the gene expression profiles of Fus-knockout hematopoietic stem/progenitor cells to understand its role in HSCs.
FET family proto-oncogene Fus contributes to self-renewal of hematopoietic stem cells.
Specimen part
View SamplesBmi1 is a component of polycomb repressive complex 1 and its role in the inheritance of the stemness of adult somatic stem cells has been well characterized. Bmi1 maintains the self-renewal capacity of adult stem cells, at least partially, by repressing the Ink4a/Arf locus that encodes a cyclin-dependent kinase inhibitor, p16Ink4a, and a tumor suppressor, p19Arf 14. Deletion of both Ink4a and Arf in Bmi1-deficient mice substantially restored the defective self-renewal capacity of HSCs and neural stem cells.
Lethal myelofibrosis induced by Bmi1-deficient hematopoietic cells unveils a tumor suppressor function of the polycomb group genes.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Forced expression of the histone demethylase Fbxl10 maintains self-renewing hematopoietic stem cells.
Specimen part
View SamplesEach fraction of mouse hematopoietic cells was purified by cell sorting from bone marrow of 8-week-old C57BL/6 mice, and its gene expression was analyzed.
Forced expression of the histone demethylase Fbxl10 maintains self-renewing hematopoietic stem cells.
Specimen part
View SamplesMouse CD34(-)KSL hematopoietic stem cells and CD34(+)KSL multipotent progenitors were purified by cell sorting from bone marrow of 8-week-old C57BL/6 mice, and their gene expression was analyzed.
Forced expression of the histone demethylase Fbxl10 maintains self-renewing hematopoietic stem cells.
Specimen part
View SamplesThe B1 SOX transcription factors SOX1/2/3/19 have been implicated in various processes of early embryogenesis. However, their regulatory functions in stages from the blastula to early neurula remain largely unknown, primarily because loss-of-function studies have not been informative to date. In our present study, we systematically knocked down the B1 sox genes in zebrafish. Only the quadruple knockdown of the four B1 sox genes sox2/3/19a/19b, which are active in the early embryo, resulted in very severe developmental abnormalities, confirming that the B1 sox genes are functionally redundant. We characterized the sox2/3/19a/19b quadruple knockdown embryos in detail by examining the changes in gene expression through microarray analysis as well as in situ hybridization.
B1 SOX coordinate cell specification with patterning and morphogenesis in the early zebrafish embryo.
Specimen part
View SamplesPericytes confer vascular stability in the retina, and the loss of pericytes can cause the blood-retina barrier breakdown seen in diabetic retinopathy. To identify endothelial-specific genes expressed in pericyte-deprived retinal vessels, we purified genetically labeled endothelial cells from Tie2-GFP transgenic mice treated with neutralizing antibody against PDGFRb (APB5) and performed gene expression profiling using DNA microarray. To find out endothelial-specific genes associated with the loss of pericyte coverage, the comparison of microarray data was carried out between retinal endothelial cells (data from GSE27238) and APB5-treated retinal endothelial cells.
Sustained inflammation after pericyte depletion induces irreversible blood-retina barrier breakdown.
Specimen part
View SamplesInfection with non-cytopathic bovine viral diarrhea virus (ncpBVDV) is associated with uterine disease and infertility. This study investigated the influence of ncpBVDV on immune functions of the bovine endometrium by testing the response to bacterial lipopolysaccharide (LPS) at the level of whole-transcriptomic gene expression. Analysis showed that approximately 30% of the 1,006 genes altered by LPS are involved in immune response. Many innate immune genes that typically respond to LPS were inhibited by ncpBVDV including those involved in pathogen recognition, inflammation, interferon response, chemokines, tissue remodeling, cell migration and cell death/survival. Infection with ncpBVDV can thus compromise immune function and pregnancy recognition thereby potentially predisposing infected cows to postpartum bacterial endometritis and reduced fertility.
Global transcriptomic profiling of bovine endometrial immune response in vitro. I. Effect of lipopolysaccharide on innate immunity.
Sex, Treatment
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