We used microarrays to observe the global gene expression in hematopoietic stem and projenitor cells during ex vivo culture with DMSO (Blank) or with Garcinol (GAR) and identified distinct classes of up or down-regulated genes.
Ex vivo expansion of human hematopoietic stem cells by garcinol, a potent inhibitor of histone acetyltransferase.
Specimen part, Treatment
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.
Poised lineage specification in multipotential hematopoietic stem and progenitor cells by the polycomb protein Bmi1.
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 polycomb group (PcG) proteins function in gene silencing through histone modifications. They form chromatin-associated multiprotein complexes, termed polycomb repressive complex (PRC) 1 and PRC2. These two complexes work in a coordinated manner in the maintenance of cellular memories through transcriptional repression of target genes. EZH2 is a catalytic component of PRC2 and trimethylates histone H3 at lysine 27 to transcriptionally repress the target genes. PcG proteins have been characterized as general regulators of stem cells, but recent works also unveiled their critical roles in cancer.
Ezh2 augments leukemogenicity by reinforcing differentiation blockage in acute myeloid leukemia.
No sample metadata fields
View SamplesAccumulating evidence suggests that mitochondrial dysfunction underlies the pathophysiology of bipolar disorder (BD) and schizophrenia (SZ). We performed large-scale DNA microarray analysis of postmortem brains of patients with BD or SZ, and examined expression patterns of mitochondria-related genes. We found a global down-regulation of mitochondrial genes, such as those encoding respiratory chain components, in BD and SZ samples, even after the effect of sample pH was controlled. However, this was likely due to the effects of medication. Medication-free patients with BD showed tendency of up-regulation of subset of mitochondrial genes. Our findings support the mitochondrial dysfunction hypothesis of BD and SZ pathologies. However, it may be the expression changes of a small fraction of mitochondrial genes rather than the global down-regulation of mitochondrial genes. Our findings warrant further study of the molecular mechanisms underlying mitochondrial dysfunction in BD and SZ.
Altered expression of mitochondria-related genes in postmortem brains of patients with bipolar disorder or schizophrenia, as revealed by large-scale DNA microarray analysis.
No sample metadata fields
View SamplesHuman embryonic stem cells (hESCs) are a powerful tool for modeling regenerative therapy. To search for the genes that promote hematopoietic development from human pluripotent stem cell, we overexpressed a list of hematopoietic regulator genes in human pluripotent stem cell-derived CD34+CD43- endothelial cells (ECs) enriched in hemogenic endothelium. Among genes tested, only SOX17, a gene encoding a transcription factor of the SOX family, promoted cell growth and supported expansion of CD34+CD43+CD45-/low cells expressing a hemogenic endothelial maker VE-cadherin. SOX17 was highly expressed in CD34+CD43- ECs but at a low level in CD34+CD43+CD45- pre-hematopoietic progenitor cells (pre-HPCs) and CD34+CD43+CD45+ HPCs. SOX17-overexpressing cells formed sphere-like colonies and generated few hematopoietic progenies. However, they retained hemogenic potential and gave rise to hematopoietic progenies upon inactivation of SOX17. Global gene expression analyses revealed that the CD34+CD43+CD45-/low cells expanded upon overexpression of SOX17 are hemogenic endothelium-like cells developmentally placed between ECs and pre-HPCs. Of interest, SOX17 also reprogrammed both pre-HPCs and HPCs into hemogenic endothelium-like cells. Genome-wide mapping of SOX17 revealed that SOX17 directly activates transcription of key regulator genes for vasculogenesis, hematopoiesis, and erythrocyte differentiation. Depletion of SOX17 in CD34+CD43- ECs severely compromised their hemogenic activity. These findings suggest that SOX17 plays a critical role in priming hemogenic potential in ECs, thereby regulates hematopoietic development from hESCs.
Role of SOX17 in hematopoietic development from human embryonic stem cells.
Specimen part, Disease
View Samples