This SuperSeries is composed of the SubSeries listed below.
MerTK Is a Functional Regulator of Myelin Phagocytosis by Human Myeloid Cells.
Specimen part, Subject
View SamplesMyeloid cells are prominent cellular constituents of the CNS. Under physiologic conditions, these include microglia within the parenchyma and systemic compartment derived macrophages localized to the perivascular spaces. Defining the relative distribution and functions of microglia versus blood-derived macrophages in the CNS parenchyma under pathologic conditions remains a challenge due to limitations in being able to distinguish these cell types. Approaches to distinguishing microglia and macrophages in experimental models include use of chimeric and parabiotic animals and molecular genetic techniques to selectively differentially label or delete a specific cell type. The current report will compare gene expression of human microglia and macrophages under distinct states of activation or polarization and relate these to their roles in tissue injury and protection /repair in the central nervous system (CNS).
MerTK Is a Functional Regulator of Myelin Phagocytosis by Human Myeloid Cells.
Specimen part, Subject
View SamplesMyeloid cells are prominent cellular constituents of the CNS. Under physiologic conditions, these include microglia within the parenchyma and systemic compartment derived macrophages localized to the perivascular spaces. Defining the relative distribution and functions of microglia versus blood-derived macrophages in the CNS parenchyma under pathologic conditions remains a challenge due to limitations in being able to distinguish these cell types. Approaches to distinguishing microglia and macrophages in experimental models include use of chimeric and parabiotic animals and molecular genetic techniques to selectively differentially label or delete a specific cell type. The current report will compare gene expression of human microglia and macrophages under distinct states of activation or polarization and relate these to their roles in tissue injury and protection /repair in the central nervous system (CNS).
MerTK Is a Functional Regulator of Myelin Phagocytosis by Human Myeloid Cells.
Specimen part, Subject
View SamplesAn important but largely unmet challenge in understanding the mechanisms that govern formation of specific organs is to decipher the complex and dynamic genetic programs exhibited by the diversity of cell types within the tissue of interest. Here, we use an integrated genetic, genomic and computational strategy to comprehensively determine the molecular identities of distinct myoblast subpopulations within the Drosophila embryonic mesoderm at the time that cell fates are initially specified. A compendium of gene expression profiles was generated for primary mesodermal cells purified by flow cytometry from appropriately staged wild-type embryos and from twelve genotypes in which myogenesis was selectively and predictably perturbed. A statistical meta-analysis of these pooled datasetsbased on expected trends in gene expression and on the relative contribution of each genotype to the detection of known muscle genesprovisionally assigned hundreds of differentially expressed genes to particular myoblast subtypes. Whole embryo in situ hybridizations were then used to validate the majority of these predictions, thereby enabling true positive detection rates to be estimated for the microarray data. This combined analysis reveals that myoblasts exhibit much greater gene expression heterogeneity and overall complexity than was previously appreciated. Moreover, it implicates the involvement of large numbers of uncharacterized, differentially expressed genes in myogenic specification and subsequent morphogenesis. These findings also underscore a requirement for considerable regulatory specificity for generating diverse myoblast identities. Finally, to illustrate how the developmental functions of newly identified myoblast genes can be efficiently surveyed, a rapid RNA interference assay that can be scored in living embryos was developed and applied to selected genes. This integrated strategy for examining embryonic gene expression and function provides a substantially expanded framework for further studies of this model developmental system.
An integrated strategy for analyzing the unique developmental programs of different myoblast subtypes.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Epigenome-wide and transcriptome-wide analyses reveal gestational diabetes is associated with alterations in the human leukocyte antigen complex.
Specimen part
View SamplesGestational diabetes mellitus (GDM) affects approximately 18% of pregnancies in the United States and increases the risk of adverse health outcomes in the offspring. These adult disease propensities may be set by anatomical and molecular alterations in the placenta associated with GDM. To assess the mechanistic aspects of fetal programming, we measured genome-wide methylation (Infinium HumanMethylation450 Beadchips) and expression (Affymetrix Transcriptome Microarrays) in placental tissue of 41 GDM cases and 41 matched pregnancies without maternal complications from the Harvard Epigenetic Birth Cohort. Specific transcriptional and epigenetic perturbations associated with GDM status included alterations in the major histocompatibility complex (MHC) region, which were validated in an independent cohort, the Rhode Island Child Health Study. Gene ontology enrichment among gene regulation influenced by GDM revealed an over-representation of immune response pathways among differential expression, reflecting these coordinated changes in the MHC region. Our study represents the largest investigation of transcriptomic and methylomic differences associated with GDM, providing comprehensive insight into the molecular basis of GDM induced fetal (re)programming.
Epigenome-wide and transcriptome-wide analyses reveal gestational diabetes is associated with alterations in the human leukocyte antigen complex.
Specimen part
View SamplesThe forkhead O transcription factors (FOXO) integrate a range of extracellular signals including growth factor signaling, inflammation, oxidative stress and nutrient availability, to substantially alter the program of gene expression and modulate cell survival, cell cycle progression, and many cell-type specific responses yet to be unraveled. Naive antigen-specific CD8+ T cells undergo a rapid expansion and arming of effector function within days of pathogen exposure, but in addition, by the peak of expansion, they form precursors to memory T cells capable of self-renewal and indefinite survival.
Differentiation of CD8 memory T cells depends on Foxo1.
Specimen part
View SamplesWe report a time course of RNA-seq data from wild-type embryonic stem cells and embryonic stem cells in which the cardiogenic transcription factors ZNF503, ZEB2 and NKX2-5 are depleted with shRNAs differentiating along the cardiac lineage. Overall design: Biological replicates of RNA-seq data from embryonic stem cells differentiating along the cardiac lineage.
An Orthologous Epigenetic Gene Expression Signature Derived from Differentiating Embryonic Stem Cells Identifies Regulators of Cardiogenesis.
No sample metadata fields
View SamplesTL1A contributes to the pathogenesis of several chronic inflammatory diseases, including Inflammatory Bowel Diseases by enhancing TH1, TH17, and TH2 responses. TL1A mediates a strong co-stimulation of these TH subsets particularly of mucosal CCR9+ T cells. However, the signaling pathways that TL1A induces in different TH subsets are incompletely understood. Here, we investigated the function of TL1A on human TH17 cells. TL1A together with TGF- IL-6, and IL-23 enhanced the secretion of IL-17 and IFN- from human CD4+ memory T cells. TL1A induced the expression of the transcription factors BATF and T-bet that correlated with the secretion of IL-17 and IFN-. In contrast, TL1A alone induced high levels of IL-22 in memory CD4+ T cells and committed TH17 cells. However, TL1A did not enhance expression of IL-17A in TH17 cells. Expression of the transcription factor aryl hydrocarbon receptor that regulates expression of IL-22 was not affected by TL1A. We performed transcriptome analysis of TH17 cells to determine genes that are transcriptionally regulated by TL1A. transcriptome analysis revealed increased expression of IL-9 in response to TL1A.
The TNF family member TL1A induces IL-22 secretion in committed human T<sub>h</sub>17 cells via IL-9 induction.
Specimen part
View SamplesCardiogenesis involves multiple biological processes acting in concert during development, a coordination achieved by the regulation of diverse cardiac genes by a finite set of transcription factors (TFs). Previous work from our laboratory identified the roles of two Forkhead TFs, Checkpoint suppressor homologue (CHES-1-like) and Jumeau (Jumu) in governing cardiac progenitor cell divisions by regulating Polo kinase activity. These TFs were also implicated in the regulation of numerous other cardiac genes. Here we show that these two Forkhead TFs play an additional and mutually redundant role in specifying the cardiac mesoderm (CM): eliminating the functions of both CHES-1-like and jumu in the same embryo results in defective hearts with missing hemisegments. Our observations indicate that this process is mediated by the Forkhead TFs regulating the fibroblast growth factor receptor Heartless (Htl) and the Wnt receptor Frizzled (Fz), both previously known to function in cardiac progenitor specification: CHES-1-like and jumu exhibit synergistic genetic interactions with htl and fz in CM specification, thereby implying function through the same genetic pathways, and transcriptionally activate the expression of both receptor-encoding genes. Furthermore, ectopic overexpression of either htl or fz in the mesoderm partially rescues the defective CM specification phenotype seen in embryos doubly homozygous for mutations in jumu and CHES-1-like. Together, these data emphasize the functional redundancy that leads to robustness in the cardiac progenitor specification process mediated by Forkhead TFs regulating the expression of signaling pathway receptors, and illustrate the pleiotropic functions of this class of TFs in different aspects of cardiogenesis.
Two forkhead transcription factors regulate the division of cardiac progenitor cells by a Polo-dependent pathway.
Specimen part
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