Erythropoiesis in mammals replenishes the circulating red blood cell (RBC) pool from hematopoietic stem/progenitor cells (HSPCs). Two distinct erythropoietic programs have been described. In the first trimester, hematopoietic precursors in the fetal yolk sac follow a primitive pattern of erythropoiesis. However, in the second trimester, hematopoietic stem cells (HSCs) from the fetal liver and later from the bone marrow differentiate by a definitive program of erythropoiesis to yield enucleated erythrocytes. RBCs can also be derived from human induced pluripotent stem cells (hiPSCs) and can express many of the red cell proteins required for normal erythrocyte function, presaging in vitro RBC production for clinical use. However, expansion and enucleation from hiPSCs is less efficient than with erythroblasts (EBs) derived from adult or cord blood progenitors. We hypothesized that substantial differential gene expression during erythroid development from hiPSCs compared to that from adult blood or cord blood precursors could account for these hitherto unexplained differences in proliferation and enucleation. We have therefore grown EBs from human adult and cord blood progenitors and from hiPSCs. Gene expression during erythroid culture from each erythroblast source was analyzed using algorithms designed to cluster co-expressed genes in an unsupervised manner and the function of differentially expressed genes explored by gene ontology. Using these methods we identify specific patterns of gene regulation for adult- and cord- derived EBs, regardless of the medium used, that are substantially distinct from those observed during the differentiation of EBs from hiPSC progenitors which largely follows a pattern of primitive erythropoiesis.
Distinct gene expression program dynamics during erythropoiesis from human induced pluripotent stem cells compared with adult and cord blood progenitors.
Specimen part
View SamplesUnderstanding the pattern of gene expression and identifying the specific genes expressed during erythropoiesis is crucial for a synthesis of erythroid developmental biology. Here we have isolated four distinct populations of erythroblasts at successive erythropoietin-dependent stages of erythropoiesis including the terminal, pyknotic stage. The transcriptome has been determined using Affymetrix arrays. First, we show that cells sorted by surface expression profile express not only significantly fewer genes than unsorted cells, but also significantly more differences in the expression levels of particular genes between stages than unsorted cells, demonstrating the importance of working with defined cell populations to identify lineage and temporally-specific patterns of gene expression. Second, using standard software and matched filtering we identify eleven differentially regulated genes and one continuously expressed gene previously undetected in erythroid expression studies with unknown roles in erythropoiesis (CA3, CALB1, CTSL2, FKBP1B, GSDMB, ITLN1, LIN7B, RRAD, RUNDC3A, UNQ1887, ZNF805, MYL12B). Finally, using transcription factor binding site analysis we identify potential transcription factors that may regulate gene expression during terminal erythropoiesis. Our stringent lists of differentially regulated and continuously expressed transcripts are a resource for functional studies of erythropoietic protein function and gene regulation.
Global gene expression analysis of human erythroid progenitors.
Specimen part
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Regulation of the ovarian inflammatory response at ovulation by nuclear progesterone receptor.
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View SamplesOvulation requires sequential molecular events and structural remodeling in the ovarian follicle for the successful release of a mature oocyte capable of being fertilised. Critical to this process is progesterone receptor (PGR), a transcription factor highly yet transiently expressed in granulosa cells of preovulatory follicles. Progesterone receptor knockout (PRKO) mice are anovulatory, with a specific and complete defect in follicle rupture. Therefore, this model was used to examine the critical molecular and biochemical mechanisms necessary for successful ovulation.
Regulation of the ovarian inflammatory response at ovulation by nuclear progesterone receptor.
No sample metadata fields
View SamplesOvulation requires sequential molecular events and structural remodeling in the ovarian follicle for the successful release of a mature oocyte capable of being fertilised. Critical to this process is progesterone receptor (PGR), a transcription factor highly yet transiently expressed in granulosa cells of preovulatory follicles. Progesterone receptor knockout (PRKO) mice are anovulatory, with a specific and complete defect in follicle rupture. Therefore, this model was used to examine the critical molecular and biochemical mechanisms necessary for successful ovulation.
Regulation of the ovarian inflammatory response at ovulation by nuclear progesterone receptor.
No sample metadata fields
View SamplesZinc is an essential micronutrient in pregnancy and zinc deficiency impairs fetal growth. We used a mouse model of moderate zinc deficiency to determine how zinc is important to placental morphogenesis.
Zinc is a critical regulator of placental morphogenesis and maternal hemodynamics during pregnancy in mice.
Specimen part
View SamplesDyskeratosis congenita (DC) is an inherited multi-system disorder, characterized by oral leukoplakia, nail dystrophy, and abnormal skin pigmentation, as well as high rates of bone marrow failure, solid tumors, and other medical problems such as osteopenia. DC and telomere biology disorders (collectively referred to as TBD here) are caused by germline mutations in telomere biology genes leading to very short telomeres and limited proliferative potential of hematopoietic stem cells. We found that skeletal stem cells (SSCs) within the bone marrow stromal cell population (BMSCs, also known as bone marrow-derived mesenchymal stem cells), may contribute to the hematological phenotype.
Molecular profile of clonal strains of human skeletal stem/progenitor cells with different potencies.
Cell line
View SamplesImmune system homeostasis depends on signals that drive effector (like secretion of pro-inflammatory cytokines like IFNg) and regulatory (like secretion of the anti-inflammatory cytokine IL-10) functions.
The cholesterol biosynthesis pathway regulates IL-10 expression in human Th1 cells.
Specimen part, Subject
View SamplesWe have previously identified a significant increase in chloroplast reactive oxygen species in wounded leaves of Arabidopsis and other plants, which is light-dependent (Flor-Henry et al. (2004) BMC Plant Biology 4:19). The aims of this study were to (i) examine the early response to mechanical wounding in Arabidopsis leaves, (ii) test the hypothesis that light-dependent chloroplast ROS may play a role in signalling for changes in gene expression in wounded leaves, and (iii) examine the broader impact of the light environment on the wound response in Arabidopsis.
Light exerts multiple levels of influence on the Arabidopsis wound response.
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View SamplesTranscriptome analyses using a wild-type strain of Saccharomyces cerevisiae were performed to assess the overall pattern of gene expression during the transition from glucose-based fermentative to glycerol-based respiratory growth. These experiments revealed a complex suite of metabolic and structural changes associated with the adaptation process. Alterations in gene expression leading to remodeling of various membrane transport systems and the cortical actin cytoskeleton were observed. Transition to respiratory growth was accompanied by alterations in transcript patterns demonstrating not only a general stress response, as seen in earlier studies, but also the oxidative and osmotic stress responses. In some contrast to earlier studies, these experiments identified modulation of expression for many genes specifying transcription factors during the transition to glycerol-based growth. Importantly and unexpectedly, an ordered series of changes was seen in transcript levels from genes encoding components of the TFIID, SAGA (Spt-Ada-Gcn5-Acetyltransferase), and SLIK (Saga LIKe) complexes and all three RNA polymerases, suggesting a modulation of structure for the basal transcriptional machinery during adaptation to respiratory growth. In concert with data given in earlier studies, the results presented here highlight important aspects of metabolic and other adaptations to respiratory growth in yeast that are common to utilization of multiple carbon sources. Importantly, they also identify aspects specific to adaptation of this organism to growth on glycerol as sole carbon source.
Transcriptome profiling of Saccharomyces cerevisiae during a transition from fermentative to glycerol-based respiratory growth reveals extensive metabolic and structural remodeling.
No sample metadata fields
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