Bone marrow mesenchymal stromal cells (MSCs) that express high levels of stem cell factor (SCF) and CXC chemokine ligand 12 (CXCL12) are one crucial component of the hematopoietic stem cell (HSC) niche. While the secreted factors produced by MSCs to support HSCs have been well described, little is known regarding the transcriptional regulators controlling the cell fate of MSCs and thus indirectly maintaining HSCs. Bmi1 is a polycomb group protein that regulates HSCs both cell intrinsically and extrinsically, but it is unknown in which cell type and how Bmi1 functions to maintain HSCs extrinsically. Here we show that Bmi1 maintains HSCs by preventing adipogenic differentiation of MSCs. Bmi1 is highly expressed in MSCs but becomes downregulated upon adipogenic differentiation and during aging. Deleting Bmi1 from MSCs increased marrow adipocytes, induced HSC quiescence and depletion, and impaired hematopoiesis. We found that Bmi1 repressed multiple developmental programs in MSCs by safeguarding the repressive epigenetic marks histone H2A ubiquitylation and H3 lysine 27 trimethylation. We identified a novel adipogenic program governed by Pax3, which Bmi1 repressed in MSCs. Our results establish Bmi1 as a critical regulator of MSC cell fate that suppresses marrow adipogenesis to create a supportive niche for HSCs. Overall design: RNA-Seq of two treatments (Ctrl, KO) with three replications per treatment.
Bmi1 Suppresses Adipogenesis in the Hematopoietic Stem Cell Niche.
Specimen part, Subject
View SamplesWe found that a number of Tfh cells downmodulated BCL6 protein after their development, and we sought to compare the gene expression between BCL6-hi Tfh cells and BCL6-low Tfh cells.
Bcl6 protein expression shapes pre-germinal center B cell dynamics and follicular helper T cell heterogeneity.
Specimen part
View SamplesTreatment of MCF7 breast cancer cells by cisplatin leads to a very specific metabolic response and an onset of cell death about 10-11 h after beginning of treatment. For more detailed understanding of the molecular processes underlying the specific metabolic response, mRNA was isolated from MCF7 cells when the specific changes, (i) induction of glycolysis and (ii) onset of cell death, were detected during online measurement in the cell biosensor system.
Real-time monitoring of cisplatin-induced cell death.
Cell line
View SamplesSpecific deletion of suppressor of cytokine signaling 3 (Socs3) in keratinocytes can cause severe skin inflammation with infiltration of immune cells, however the molecular mechanisms and key regulatory pathways involved remains poorly understood. To investigate the role of Socs3 in keratinocytes, we generated and analyzed global RNA-Seq profiles in Socs3 conditional knockout (cKO) mice at two different stages (2- and 10- weeks). Over 400 shared genes were found to be significantly regulated at both time points. Two week samples were marked by initial skin barrier dysfunction established by the downregulation of keratin associated genes and upregulation of genes regulating lipid metabolism. Subsequent increase in expression level of multiple chemokines and cytokines at 10 week were observed representing response to skin inflammation caused by the disruption of skin barrier function. A group of activator protein-1 related genes were to found to be highly elevated in Socs3 cKO mice at both time points. This observation was duly validated using qRT-PCR in Socs3 depleted human keratinocyte–derived HaCaT cells. Overall this study reveals an important regulatory dynamics of Socs3 in skin barrier dysfunction. Overall design: Socs3 cKO mice mRNA profiles of 2 and 10 week wild type (WT) C57BL/6 mice were generated by sequencing using HiSeq 1000 system (Illumina) machine which could read a 50 bp sequence.
Insights into gene expression profiles induced by Socs3 depletion in keratinocytes.
Age, Specimen part, Cell line, Subject
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 SamplesAnalysis of whole gene expression during differentiation from hiPS cells into hepatocyte-like cells. The hypothesis tested in the present study was that the hepatocyte-like cells induced with adrenergic receptor agonists were identical to those induced with conventional growth factors (hepatocyte growth factor and oncostatin M). Results provide the important information of the differentiation mechanisms from hepatoblasts into hepatocytes. Overall design: Total RNA obtained from undifferentiated hiPS cells, hiPS cell-derived hepatoblast-like and hepatocyte-like cells. The hiPS cells were induced to differentiate into hepatoblast-like cells, then the cells were treated with methoxamine or growth factors (hepatocyte growth factor and oncostatin M) to induce the differentiation into hepatocyte-like cells.
Adrenergic receptor agonists induce the differentiation of pluripotent stem cell-derived hepatoblasts into hepatocyte-like cells.
Sex, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Tbx3-dependent amplifying stem cell progeny drives interfollicular epidermal expansion during pregnancy and regeneration.
Sex, Specimen part
View SamplesTo identify genes expressed predominantly in the ventral skin epidermal basal cells of pregnant mice, we performed DNA microarray analysis by using FACS-purified epidermal basal cells from ventral skin at 0 and 16 dpc, and dorsal skin at 16 dpc.
Tbx3-dependent amplifying stem cell progeny drives interfollicular epidermal expansion during pregnancy and regeneration.
Sex, Specimen part
View SamplesTo identify genes expressed predominantly in the ventral skin dermis of pregnant mice, we performed DNA microarray analysis by using isolated dermal tissues from ventral skin at 0 and 15 dpc, PP2-injected ventral skin at 15 dpc, and dorsal skin at 15 dpc.
Tbx3-dependent amplifying stem cell progeny drives interfollicular epidermal expansion during pregnancy and regeneration.
Sex, Specimen part
View SamplesAire in medullary thymic epithelial cells plays an essential role in the negative selection through expression of broad arrays of tissue-restricted antigens.
Ectopic Aire Expression in the Thymic Cortex Reveals Inherent Properties of Aire as a Tolerogenic Factor within the Medulla.
Specimen part, Disease
View Samples